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Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger

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(1)Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger Mulder, H.J.. Citation Mulder, H. J. (2010, February 2). Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger. Retrieved from https://hdl.handle.net/1887/14647 Version:. Corrected Publisher’s Version. License:. Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden. Downloaded from:. https://hdl.handle.net/1887/14647. Note: To cite this publication please use the final published version (if applicable)..

(2)  Chapter1     GeneralIntroduction.

(3) Chapter1.  GeneralIntroduction  —‰‹ ’‡”ˆ‘” –Š‡ ‡••‡–‹ƒŽ ”‘Ž‡ ‘ˆ †‡ ‘’‘•‹‰ ‘”‰ƒ‹  ƒ––‡” ‹ ƒ–—”‡ǡ ƒ† ƒ”‡ ‹†‹•’‡•ƒ„Ž‡ ‹ —–”‹‡– › Ž‹‰ ƒ† ‡š Šƒ‰‡Ǥ ‘‰‡–Š‡” ™‹–Š –Š‡ ‹ƒŽ‹ƒǡ Žƒ–ƒ‡ ƒ† ”‘–‹•–ƒǡ —‰‹ ‘’‘•‡–Š‡ˆ‘—”‹‰†‘•‘ˆ‡—ƒ”›‘–‹ ‘”‰ƒ‹••Ǥ Aspergillus niger ‹• ƒ •‘‹Ž †™‡ŽŽ‹‰ ˆ‹Žƒ‡–‘—• ˆ—‰—• –Šƒ– ‹• —„‹“—‹–‘—• ‹ •‘‹Ž• ™‘”Ž†™‹†‡Ǥ‡‹‰ƒ•ƒ’”‘’Š›–‹ ‘”‰ƒ‹•‹–’Žƒ›•ƒ‹’‘”–ƒ–”‘Ž‡‹–Š‡†‡‰”ƒ†ƒ–‹‘ƒ† ”‡ › Ž‹‰ ‘ˆ ‘”‰ƒ‹  †‡„”‹• •— Š ƒ• ’Žƒ– ‡ŽŽǦ™ƒŽŽ ƒ–‡”‹ƒŽǤ Š‡ •ƒ’”‘’Š›–‹  ƒ–—”‡ ‘ˆ A. niger ”‡“—‹”‡• –Š‡ ƒ„—†ƒ– •‡ ”‡–‹‘ ‘ˆ ƒ ˜ƒ”‹‡–› ‡œ›‡• –‘ †‡‰”ƒ†‡ ƒ† ‡š–”ƒ – —–”‹‡–• ˆ”‘ ‘’Ž‡š ’‘Ž›‡”‹  •—„•–”ƒ–‡•Ǥ Š‡ ”‡Ž‡ƒ•‡† •—‰ƒ”• ƒ ‡‹–Š‡” „‡ ‡–ƒ„‘Ž‹•‡†–‘•—•–ƒ‹‰”‘™–Šǡ‘”—†‡” ‡”–ƒ‹ ‘†‹–‹‘•„‡ ‘˜‡”–‡†‹–‘‘”‰ƒ‹ ƒ ‹†• Ž‹‡ ‹–”‹  ƒ ‹† ™Š‹ Š –Š‡ ˆ—‰—• ƒ ”‡Ǧ—•‡ Žƒ–‡”Ǥ ‹‡ ‘–Š‡” ˆ‹Žƒ‡–‘—• ˆ—‰‹ǡ A. niger ‰”‘™•‹–Š‡˜‡‰‡–ƒ–‹˜‡’Šƒ•‡‘ˆ‹–•Ž‹ˆ‡ › Ž‡„›ˆ‘”‹‰–—„—Žƒ”•Šƒ’‡† ‡ŽŽ• ƒŽŽ‡†Š›’Šƒ‡Ǥ Š›’Šƒ‹•—•—ƒŽŽ›ƒ†‡—’‘ˆ—Ž–‹’Ž‡ ‡ŽŽ•ǡ•‡’ƒ”ƒ–‡†„›•‡’–ƒǤŠ‡•‡Š›’Šƒ‡‡š–‡†ƒ– –Š‡‹” ƒ’‹ ‡•ǡ ƒ† „”ƒ Š •—„ƒ’‹ ƒŽŽ› ”‡•—Ž–‹‰ ‹ ƒ ‡–™‘” ‘ˆ Š›’Šƒ‡ ‡š–‡†‹‰ ‹ ƒŽŽ †‹”‡ –‹‘•Ǥ”‘–‡‹•‡ ”‡–‹‘‘ —”•‘•–Ž›ƒ––Š‡Š›’ŠƒŽ–‹’ǡƒ†–‘‰‡–Š‡”™‹–Š–Š‡ƒ’‹ ƒŽ ‡š–‡•‹‘‘ˆ–Š‡Š›’Šƒ‡ǡ–Š‹•ƒŽŽ‘™•–Š‡ˆ—‰—•–‘’‡‡–”ƒ–‡ƒ††‹‰‡•–•‘Ž‹†•—„•–”ƒ–‡•Ǥ   TheIndustrialUseofAspergillusniger Š‡ƒ„‹Ž‹–›‘ˆA.niger–‘’”‘†— ‡ ‹–”‹ ƒ ‹†™ƒ•†‹• ‘˜‡”‡†„› ƒ‡•—””‹‡‹ͳͻͳ͹ǡƒ† Šƒ• „‡‡ ‡š’Ž‘‹–‡† „› –Š‡ ‹†—•–”› •‹ ‡ ͳͻͳͻǤ Š‡ ƒ„‹Ž‹–› –‘ •‡ ”‡–‡ Žƒ”‰‡ ƒ‘—–• ‘ˆ ‡œ›‡• ‹–‘ –Š‡ ‡˜‹”‘‡– Šƒ• „‡‡ —–‹Ž‹•‡† •‹ ‡ –Š‡ ͳͻ͸Ͳ• ˆ‘” –Š‡ ’”‘†— –‹‘ ‘ˆ ‡œ›‡• ˆ‘” –Š‡ •–ƒ” Š ’”‘ ‡••‹‰ ƒ† ˆ‘‘† ‹†—•–”› ͳͶ͸Ǥ Š‡ Ž‘‰ —•‡ ‘ˆ A. niger ‹ –Š‡ ‹†—•–”›ˆ‘”’”‘†— –‹‘‘ˆˆ‘‘†‡œ›‡•ƒ† ‹–”‹ ƒ ‹†Šƒ•Ž‡†–‘–Š‡ •–ƒ–—•‘ˆƒ› ‘ˆ –Š‡ ’”‘†— –• ’”‘†— ‡† „› A. niger ȋǤǤ ‘‘† ƒ† ”—‰ †‹‹•–”ƒ–‹‘Ǥ Š––’ǣȀȀ™™™Ǥ ˆ•ƒǤˆ†ƒǤ‰‘˜Ȁ̱”†„Ȁ‘’ƒǦ‰”ƒ•ǤŠ–ŽȌǤ Š‡ ’”‘‰”‡•• ‹ ‰‡‡–‹  ƒ‹’—Žƒ–‹‘ ‘ˆ ˆ‹Žƒ‡–‘—• ˆ—‰‹ ‘– ‘Ž› Ž‡† –‘ –Š‡ ‘’–‹‹•ƒ–‹‘‘ˆ–Š‡’”‘†— –‹‘‘ˆŠ‘‘Ž‘‰‘—•’”‘–‡‹• ͳ͹Ͳǡ„—–ƒŽ•‘’”‘˜‹†‡†’‘••‹„‹Ž‹–‹‡• ˆ‘”—•‹‰ˆ‹Žƒ‡–‘—•ˆ—‰‹ˆ‘”–Š‡’”‘†— –‹‘‘ˆŠ‡–‡”‘Ž‘‰‘—•’”‘–‡‹•‘ˆ„‘–Šˆ—‰ƒŽƒ† ‘Ǧˆ—‰ƒŽ ‘”‹‰‹Ǥ ‘™‡˜‡”ǡ ™Š‡”‡ƒ• Žƒ”‰‡ ƒ‘—–• ‘ˆ Š‘‘Ž‘‰‘—• ’”‘–‡‹• ƒ „‡ ‘„–ƒ‹‡† ‹ ‹†—•–”‹ƒŽ ˆ‡”‡–ƒ–‹‘•ǡ –Š‡ ’”‘†— –‹‘ ›‹‡Ž†• ˆ‘” Š‡–‡”‘Ž‘‰‘—• ’”‘–‡‹• ‘ˆ ‘Ǧˆ—‰ƒŽ‘”‹‰‹ƒ”‡–›’‹ ƒŽŽ›•‡˜‡”ƒŽ‘”†‡”•‘ˆƒ‰‹–—†‡Ž‘™‡”ͳʹͻǡͳ͸͹Ǥ ›†‹••‡ –‹‰–Š‡•–‡’•‹˜‘Ž˜‡†‹•›–Š‡•‹•ƒ†•‡ ”‡–‹‘‘ˆ’”‘–‡‹•‡˜‡”ƒŽˆƒ –‘”• ‹ˆŽ—‡ ‹‰ –Š‡ •‡ ”‡–‹‘ Ž‡˜‡Ž Šƒ˜‡ „‡‡ ‹†‡–‹ˆ‹‡†Ǥ ”‘–‡‹ •›–Š‡•‹• ƒ „‡ Ž‹‹–‡† ƒ– ‡˜‡”› Ž‡˜‡Ž ‹ –Š‡ ’”‘ ‡••Ǣ ˆ”‘ –Š‡ –”ƒ• ”‹’–‹‘ƒŽǡ –”ƒ•Žƒ–‹‘ƒŽ ƒ† ’‘•–Ǧ–”ƒ•Žƒ–‹‘ƒŽ Ž‡˜‡Ž –‘ –Š‡ •‡ ”‡–‘”› ƒ† ’‘•–Ǧ•‡ ”‡–‘”› Ž‡˜‡ŽǤ ƒ –‘”• –Šƒ– ƒ ‡‰ƒ–‹˜‡Ž› ‹ˆŽ—‡ ‡ –Š‡ 10GeneralIntroduction.

(4) Chapter1 ˆ‹ƒŽ’”‘†— –‹‘Ž‡˜‡Žƒ”‡ǣȋͳȌ•–ƒ„‹Ž‹–›ǡȋʹȌ ‘†‘—•ƒ‰‡ǡȋ͵Ȍ‹‡ˆˆ‹ ‹‡––”ƒ•Ž‘ ƒ–‹‘ǡ ˆ‘Ž†‹‰ƒ†–”ƒ•’‘”––Š”‘—‰Š–Š‡•‡ ”‡–‹‘’ƒ–Š™ƒ›ƒ†ȋͶȌ‡š–”ƒ ‡ŽŽ—Žƒ”†‡‰”ƒ†ƒ–‹‘Ͷ͹Ǥ —„‡”‘ˆ•–”ƒ–‡‰‹‡•ƒ††”‡••‹‰–Š‘•‡Ž‹‹–ƒ–‹‘•Šƒ˜‡„‡‡ƒ’’Ž‹‡†‹‘”†‡”–‘‘’–‹‹•‡ ‘”‹ ”‡ƒ•‡Š‡–‡”‘Ž‘‰‘—•’”‘–‡‹’”‘†— –‹‘„›ˆ‹Žƒ‡–‘—•ˆ—‰‹Ǥ‘‰–Š‘•‡•–”ƒ–‡‰‹‡• ƒ”‡ –Š‡ —•‡ ‘ˆ •–”‘‰ Š‘‘Ž‘‰‘—• ’”‘‘–‡”•ǡ –Š‡ —•‡ ‘ˆ —Ž–‹ ‘’› –”ƒ•ˆ‘”ƒ–•ǡ ‘ˆ ’”‘–‡ƒ•‡Ǧ†‡ˆ‹ ‹‡– Š‘•– •–”ƒ‹•ǡ –Š‡ ‹–”‘†— –‹‘ ‘ˆ ‡ˆˆ‹ ‹‡– •‡ ”‡–‹‘ •‹‰ƒŽ•ǡ –Š‡ —•‡ ‘ˆ ™‡ŽŽǦ•‡ ”‡–‡†’”‘–‡‹•ƒ• ƒ””‹‡”•ǡƒ†–Š‡‘˜‡”Ǧ‡š’”‡••‹‘‘ˆˆ‘Ž†ƒ•‡•ƒ†Ȁ‘” Šƒ’‡”‘‡• ʹǡͶ͹Ǥ. Š‡ ”‹‰Š– ‘„‹ƒ–‹‘ ‘ˆ –Š‡ ƒ„‘˜‡ ‡–‹‘‡† ƒ’’”‘ƒ Š‡• –‘‰‡–Š‡” ™‹–Š Žƒ••‹ ƒŽ. •–”ƒ‹‹’”‘˜‡‡– ƒ‹ ”‡ƒ•‡–Š‡’”‘†— –‹‘›‹‡Ž†ˆ‘”•‘‡Š‡–‡”‘Ž‘‰‘—•’”‘–‡‹•ǡ„—– ‘ˆ–‡‘–—’–‘–Š‡Ž‡˜‡Ž•‘ˆŠ‘‘Ž‘‰‘—•’”‘–‡‹’”‘†— –‹‘Ͷ͹Ǥ Š‡‡š’”‡••‹‘‘ˆƒŠ‡–‡”‘Ž‘‰‘—•’”‘–‡‹‘ˆ–‡‹•ƒ ‘’ƒ‹‡†„›ƒ—’”‡‰—Žƒ–‹‘ ‘ˆŽ‘ ƒŽ‹•‡†ˆ‘Ž†ƒ•‡•Ǥ”‘–‡‹•‡ ”‡–‹‘ƒ†‹’ƒ”–‹ —Žƒ”’”‘–‡‹ˆ‘Ž†‹‰ƒ†ƒ–—”ƒ–‹‘ ‹ –Š‡ ‡†‘’Žƒ•‹  ”‡–‹ —Ž— ȋȌ ‹• –Š‡”‡ˆ‘”‡ ”‡‰ƒ”†‡† ƒ• –Š‡ ƒŒ‘” „‘––Ž‡‡  ‹ Š‡–‡”‘Ž‘‰‘—• ’”‘–‡‹ ’”‘†— –‹‘ „› ˆ‹Žƒ‡–‘—• ˆ—‰‹ ʹǡͳ͹ǡͶ͹ǡͳʹͲǡͳ͵ͻǤ Š‡ ‡ˆˆ‘”–• –‘ ‹’”‘˜‡ Š‡–‡”‘Ž‘‰‘—• ’”‘–‡‹ ’”‘†— –‹‘ ‹ ˆ‹Žƒ‡–‘—• ˆ—‰‹ ˆ‘ —•‡• –Š‡”‡ˆ‘”‡ ‘•–Ž› ‘ –Š‡ •‡ ”‡–‘”›’ƒ–Š™ƒ›ƒ†–Š‡ˆ‘Ž†‹‰‘ˆ’”‘–‡‹•‹–Š‡‹’ƒ”–‹ —Žƒ”Ǥ   TheSecretoryPathway —ƒ”›‘–‹  ‡ŽŽ• ’‘••‡•• ƒ •‡ ”‡–‘”› ’ƒ–Š™ƒ› –Šƒ– ‹• ƒ†‡ —’ ‘ˆ ƒ ‡Žƒ„‘”ƒ–‡ ‡†‘‡„”ƒ‡ ‡–™‘”Ǥ Š‹• ‡–™‘” ‘•‹•–• ‘ˆ •‡˜‡”ƒŽ ‹†‡’‡†‡– ‘”‰ƒ‡ŽŽ‡• –Šƒ– ƒ‡—’ƒƒ••‡„Ž›Ž‹‡ˆ‘”–Š‡’”‘†— –‹‘‘ˆ•‡ ”‡–‘”›’”‘–‡‹•ƒ†’”‘–‡‹•™‹–Š‘–Š‡” ‡ŽŽ—Žƒ” †‡•–‹ƒ–‹‘• •— Š ƒ• –Š‡ ‡ŽŽ ‡„”ƒ‡Ǥ ƒ Š ‘’ƒ”–‡– ‹ –Š‡ •‡ ”‡–‘”› ’ƒ–Š™ƒ› ’”‘˜‹†‡• ƒ •’‡ ‹ƒŽ‹•‡† ‡˜‹”‘‡– –Šƒ– ˆƒ ‹Ž‹–ƒ–‡• –Š‡ ˜ƒ”‹‘—• •–ƒ‰‡• ‹ ’”‘–‡‹ „‹‘‰‡‡•‹•ǡ‘†‹ˆ‹ ƒ–‹‘ǡ•‘”–‹‰ƒ†ˆ‹ƒŽŽ›•‡ ”‡–‹‘‹–‘–Š‡‡˜‹”‘‡–Ǥ Š‡ Š‹‰Š ƒ’ƒ ‹–› ‘ˆ –Š‡ •‡ ”‡–‘”› •›•–‡ ‘ˆ A. niger ƒ† ‘–Š‡” ˆ‹Žƒ‡–‘—• ˆ—‰‹ǡ Šƒ• „‡‡ ‡š’Ž‘‹–‡† ˆ‘” †‡ ƒ†‡• „› –Š‡ ‹†—•–”› ˆ‘” –Š‡ ’”‘†— –‹‘ ‘ˆ ’”‘–‡‹• ƒ† ‡–ƒ„‘Ž‹–‡•ǡ„—–†‡•’‹–‡–Š‡‹–‡•‡‰‡‡–‹ ”‡•‡ƒ” Š‘–Š‡’”‘–‡‹•‡ ”‡–‹‘‡ Šƒ‹• ‹ ˆ‹Žƒ‡–‘—• ˆ—‰‹ǡ –Š‡ ‘™Ž‡†‰‡ ‘ˆ –Š‡ ˆ—‰ƒŽ •‡ ”‡–‘”› ’ƒ–Š™ƒ› Šƒ• „‡‡ Ž‹‹–‡†Ǥ ‘™‡˜‡”ǡ –Š‡ ƒ˜ƒ‹Žƒ„‹Ž‹–› ‘ˆ –Š‡ ™Š‘Ž‡ ‰‡‘‡ •‡“—‡ ‡ ‘ˆ •‡˜‡”ƒŽ ˆ‹Žƒ‡–‘—• ˆ—‰‹ǡ ‹ Ž—†‹‰–Š‡‹†—•–”‹ƒŽ‹’‘”–ƒ–•’‡ ‹‡•Aspergillusoryzae ͺ͹ƒ†A.niger ͳʹ͸ǡŠƒ˜‡ƒ†‡ ˆ‘”ƒŽ ‰‡‘‹ • ƒ’’”‘ƒ Š‡• –‘ –Š‡ •–—†› ‘ˆ ’”‘–‡‹ •‡ ”‡–‹‘ ‹ –Š‘•‡ ‘”‰ƒ‹•• ‘”‡ ˆ‡ƒ•‹„Ž‡Ǥ

(5) –‹•‰‡‡”ƒŽŽ›ƒ ‡’–‡†–Šƒ––Š‡•‡ ”‡–‘”›’ƒ–Š™ƒ›‹ˆ‹Žƒ‡–‘—•ˆ—‰‹†‘‡•‘– †‹ˆˆ‡”‰”‡ƒ–Ž›ˆ”‘–Š‘•‡‹›‡ƒ•–ƒ†Š‹‰Š‡”‡—ƒ”›‘–‡•ǡ™Š‹ ŠŠƒ˜‡„‡‡•–—†‹‡†‹‘”‡ †‡–ƒ‹ŽǤ Š‡ †‹ˆˆ‡”‡ ‡• Žƒ› ƒ‹Ž› ‹ –Š‡ ’‘Žƒ” ‰”‘™–Š ‘ˆ ˆ‹Žƒ‡–‘—• ˆ—‰‹Ǥ Š‡ › ‡Ž‹ƒŽ ‰”‘™–Š ’Š‡‘–›’‡ ‘ˆ ˆ‹Žƒ‡–‘—• ˆ—‰‹ǡ ™Š‹ Š ‘•‹•– ‘ˆ —Ž–‹Ǧ ‡ŽŽ—Žƒ” –—„—Žƒ” Š›’Šƒ‡ ƒ†‡—’‘ˆ ›Ž‹†”‹ ƒŽ ‘’ƒ”–‡–•†‹˜‹†‡†„›’‡”ˆ‘”ƒ–‡†•‡’–ƒǡ‹•‘–ˆ‘—†‹›‡ƒ•–‘” Š‹‰Š‡”‡—ƒ”›‘–‡•ǤŽ•‘ǡ’”‘–‡‹•‡ ”‡–‹‘‹ˆ‹Žƒ‡–‘—•ˆ—‰‹‹•„‡Ž‹‡˜‡†–‘‘ —”ƒ‹Ž› ƒ––Š‡Š›’ŠƒŽ–‹’‘”•—„Ǧƒ’‹ ƒŽŠ›’ŠƒŽ”‡‰‹‘• Ͷ͸ǡͳͺʹǤ‘„‡•‹†‡•–Š‡ ƒ’ƒ ‹–›‘ˆ–Š‡’”‘–‡‹ GeneralIntroduction11.

(6) Chapter1 •‡ ”‡–‹‘ ’ƒ–Š™ƒ›ǡ ™Š‹ Š ‹• — Š Š‹‰Š‡” –Šƒ ‹ ›‡ƒ•–ǡ –Š‡ •‡ ”‡–‘”› ’ƒ–Š™ƒ› ‘ˆ ˆ‹Žƒ‡–‘—• ˆ—‰‹ •–ƒ†• ‘—– ‘•–Ž› „› –Š‡ †‹”‡ –‹‘ƒŽ‹–› ‘ˆ –Š‡ ’ƒ–Š™ƒ› †—‡ –‘ Š›’ŠƒŽ ‰”‘™–ŠǤ Š‡•‡ ”‡–‘”›’ƒ–Š™ƒ›‹ˆ‹Žƒ‡–‘—•ˆ—‰‹Šƒ•„‡‡”‡˜‹‡™‡†„› •‡˜‡”ƒŽ ƒ—–Š‘”• ͳͺǡͳʹͷǡͳͶͻǤ ‡ ”‡–‘”› ’”‘–‡‹• ‡–‡” –Š‡ ‡†‘’Žƒ•‹  ”‡–‹ —Ž— ȋȌ —’‘ –”ƒ•Žƒ–‹‘ǡ ƒ†. †—”‹‰–”ƒ•‹––Š”‘—‰Š–Š‹• ‘’ƒ”–‡––Š‡›ƒ”‡ˆ‘Ž†‡†‹–‘–Š‡‹”–‡”–‹ƒ”›ƒ†“—ƒ–‡”ƒ”› •–”— –—”‡ǡƒ†—†‡”‰‘‘†‹ˆ‹ ƒ–‹‘‹ˆ‡ ‡••ƒ”›ǤŠ‡‘†‹ˆ‹ ƒ–‹‘•‹ Ž—†‡•‹‰ƒŽ’‡’–‹†‡ ’”‘ ‡••‹‰ǡ†‹•—Žˆ‹†‡„”‹†‰‡ˆ‘”ƒ–‹‘ǡ‰Ž› ‘•›Žƒ–‹‘ǡƒ†’Š‘•’Š‘”›Žƒ–‹‘Ǥ‘””‡ –Ž›ˆ‘Ž†‡† ’”‘–‡‹•ƒ”‡•‘”–‡†‹–‘ ‘ƒ–‹‰Ǧ’”‘–‡‹Ǧ

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(8) ˜‡•‹ Ž‡•ȋ

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(10) Ȍƒ†–”ƒ•’‘”–‡†ˆ”‘–Š‡–‘ –Š‡ ‘Ž‰‹ǦŽ‹‡ •–”— –—”‡ ™Š‡”‡ ˆ—”–Š‡” ‘†‹ˆ‹ ƒ–‹‘• ‘ —”ǡ ‹ Ž—†‹‰ ‰Ž› ‘•›Žƒ–‹‘ ƒ† ’‡’–‹†‡ ’”‘ ‡••‹‰Ǥ Š‡ ƒ–—”‡ ’”‘–‡‹• ƒ”‡ ˆ‹ƒŽŽ› ’ƒ ‡† ‹–‘ •‡ ”‡–‘”› ˜‡•‹ Ž‡• ƒ† †‹”‡ –‡† –‘ –Š‡ ’Žƒ•ƒ ‡„”ƒ‡ ƒ– –Š‡ Š›’ŠƒŽ –‹’ ™Š‡”‡ –Š‡› ƒ”‡ •‡ ”‡–‡† –‘ –Š‡ ‡š–”ƒ ‡ŽŽ—Žƒ”•’ƒ ‡Ǥ‡”‹ƒŽŽ›‹•ˆ‘Ž†‡†’”‘–‡‹•‘–Š‡‘–Š‡”Šƒ†ƒ”‡”‡‘˜‡†ˆ”‘–Š‡ „›”‡–”‘Ǧ–”ƒ•Ž‘ ƒ–‹‘ƒ††‡‰”ƒ†‡†‹–Š‡ ›–‘•‘Ž„›–Š‡ʹ͸’”‘–‡ƒ•‘‡‹ƒ’”‘ ‡•• ƒŽŽ‡†Ǧƒ••‘ ‹ƒ–‡††‡‰”ƒ†ƒ–‹‘ȋȌǤ• Š‡ƒ–‹ ‘˜‡”˜‹‡™‘ˆ–Š‡•‡ ”‡–‹‘’ƒ–Š™ƒ› ‹ˆ‹Žƒ‡–‘—•ˆ—‰‹‹•‰‹˜‡‹ ‹‰—”‡ͳǡƒ††‡• ”‹„‡†‹‘”‡†‡–ƒ‹Ž„‡Ž‘™Ǥ         Figure1.Š‡•‡ ”‡–‹‘’ƒ–Š™ƒ›‹ˆ‹Žƒ‡–‘—•ˆ—‰‹Ǥ‡™Ž›•›–Š‡•‹œ‡†’‘Ž›’‡’–‹†‡•—†‡”‰‘ ˆ‘Ž†‹‰ƒ†‘†‹ˆ‹ ƒ–‹‘•‹–Š‡ǤŽ› ‘””‡ –Ž›ˆ‘Ž†‡†’”‘–‡‹•Ž‡ƒ˜‡–Š‡ȋ‹˜‡•‹ Ž‡•Ȍƒ† ‡–‡”–Š‡ ‘Ž‰‹ǦŽ‹‡•–”— –—”‡ǤŠ‡”‡–Š‡’”‘–‡‹•—†‡”‰‘ˆ—”–Š‡”‘†‹ˆ‹ ƒ–‹‘•ƒ†ƒ”‡ˆ‹ƒŽŽ› •‡ ”‡–‡†ˆ”‘–Š‡ƒ’‹ ƒŽ‘”•—„ƒ’‹ ƒŽŠ›’ŠƒŽ”‡‰‹‘•Ǥǣ— Ž‡—•Ǥǣ†‘’Žƒ•‹ ”‡–‹ —Ž—Ǥǣ ›–‘’Žƒ•‹ ˜‡•‹ Ž‡•Ǥ ǣ ‘Ž‰‹ȋǦŽ‹‡Ȍ ‘’ƒ”–‡–Ǥǣƒ —‘Ž‡Ǥǣ‡ŽŽ™ƒŽŽͶ͹Ǥ.   ERTargetingandTranslocation ”‘–‡‹ •›–Š‡•‹• •–ƒ”–• ‹ –Š‡ ›–‘•‘Ž ™Š‡”‡ ”‹„‘•‘‡• ƒ’–—”‡  ‘Ž‡ —Ž‡•ǡ ƒ† „‡‰‹–”ƒ•Žƒ–‹‘Ǥ”‘–‡‹•†‡•–‹‡†ˆ‘”–Š‡•‡ ”‡–‘”›’ƒ–Š™ƒ› ƒ„‡†‹”‡ –‡†–‘–Š‡‹ –™‘ ™ƒ›•Ǣ ‡‹–Š‡” ‘Ǧ–”ƒ•Žƒ–‹‘ƒŽ ‘” ’‘•– –”ƒ•Žƒ–‹‘ƒŽ ͳ͵ͳǤ Š‡ ‘Ǧ–”ƒ•Žƒ–‹‘ƒŽ ’ƒ–Š™ƒ› ’”‡†‘‹ƒ–‡• ‹ ‘•– ƒƒŽ‹ƒ ‡ŽŽ•ǡ ™Š‡”‡ƒ• ‹ S. cerevisiae „‘–Š ”‘—–‡• ƒ”‡ —•‡† ‡š–‡•‹˜‡Ž›ǤŠ‡”‘—–‡–Šƒ–‹•ˆ‘ŽŽ‘™‡†‹•†‡–‡”‹‡†„›–Š‡Š›†”‘’Š‘„‹  ‘”‡‘ˆ‹–••‹‰ƒŽ •‡“—‡ ‡ ͳͲ͵Ǥ

(11) – ™ƒ• ˆ‘—† –Šƒ– ’”‘–‡‹• ™‹–Š ƒ Ž‡•• Š›†”‘’Š‘„‹  •‹‰ƒŽ •‡“—‡ ‡ ™‡”‡ 12GeneralIntroduction.

(12) Chapter1 –ƒ”‰‡–‡† –Š”‘—‰Š –Š‡ •‘ ƒŽŽ‡† Ǧ‹†‡’‡†‡– ”‘—–‡ǡ ™Š‡”‡ƒ• „‘–Š ”‘—–‡• ‘—Ž† „‡ ˆ‘ŽŽ‘™‡†™Š‡ƒ‘”‡Š›†”‘’Š‘„‹ •‹‰ƒŽ™ƒ•’”‡•‡–Ǥ

(13) –Š‡ ‘Ǧ–”ƒ•Žƒ–‹‘ƒŽ–”ƒ•Ž‘ ƒ–‹‘ǡƒǦ–‡”‹ƒŽ•‹‰ƒŽ•‡“—‡ ‡ǡ™Š‹ Š ‘•‹•–• ‘ˆͳ͵Ǧ͵Ͳƒ‹‘ƒ ‹†•ǡ‹•„‘—†„›ƒ ›–‘•‘Ž‹ •‹‰ƒŽ”‡ ‘‰‹–‹‘’ƒ”–‹ Ž‡ȋȌǡƒ••‘‘ƒ•‹– Šƒ•‡‡”‰‡†ˆ”‘–Š‡”‹„‘•‘‡ǤŠ‡–”ƒ•Žƒ–‹‘’ƒ—•‡•ƒ†–Š‡ ‘’Ž‡šȋǡƒ• ‡– ’‡’–‹†‡ Šƒ‹ǡ”‹„‘•‘‡ƒ†Ȍ‹•†‹”‡ –‡†–‘–Š‡‡„”ƒ‡˜‹ƒƒ‹–‡”ƒ –‹‘™‹–Šƒ ”‡ ‡’–‘”ȋȌǤˆ–‡”†‘ ‹‰ǡ–Š‡‹•”‡Ž‡ƒ•‡†ˆ”‘–Š‡ ‘’Ž‡šƒ†–Š‡ƒ• ‡– ’‘Ž›’‡’–‹†‡ Šƒ‹‹•’ƒ••‡†–Š”‘—‰Šƒ’”‘–‡‹–”ƒ•Ž‘ ƒ–‹‘ ‘’Ž‡š‘–Š‡‡„”ƒ‡ —’‘ ‡Ž‘‰ƒ–‹‘ ͳ͵ͳǤ  ‡ –Š‡ ’‘Ž›’‡’–‹†‡ Šƒ‹ ‹• ‘’Ž‡–‡†ǡ –Š‡ •‹‰ƒŽ •‡“—‡ ‡ ‹• Ž‡ƒ˜‡†‘ˆˆƒ†–Š‡‹ƒ–—”‡’”‘–‡‹‹•”‡Ž‡ƒ•‡†‹–‘–Š‡Ž—‡Ǥ ‘•––”ƒ•Žƒ–‹‘ƒŽ –”ƒ•Ž‘ ƒ–‹‘ ‹• ‹†‡’‡†‡– ‘ˆ –Š‡ ǡ ƒ† –Š‡ –”ƒ•Ž‘ ƒ–‹‘ ‘ˆ ’”‘–‡‹•‘˜‡”–Š‡‡„”ƒ‡‘ —”•ˆ‹”•–ƒˆ–‡”–Š‡’‘Ž›’‡’–‹†‡Šƒ•„‡‡ˆ—ŽŽ›–”ƒ•Žƒ–‡†Ǥ Š‹•ƒŽ–‡”ƒ–‹˜‡”‘—–‡‘ˆ–ƒ”‰‡–‹‰’”‘–‡‹•–‘–Š‡‡„”ƒ‡‹•–Š‘—‰Š––‘ƒŽ•‘‘ —”‹ ˆ‹Žƒ‡–‘—• ˆ—‰‹Ǥ ˆ–‡” •›–Š‡•‹• ‹ –Š‡ ›–‘’Žƒ•ǡ –Š‡ ƒ• ‡– ’”‘–‡‹ ˆ‘”• ƒ ‘’Ž‡š ™‹–Š–Š‡ ›–‘•‘Ž‹  •’͹Ͳ Šƒ’‡”‘‡ƒ† ‘Ǧ Šƒ’‡”‘‡•–‘‡‡’‹–‹ƒ—ˆ‘Ž†‡†•–ƒ–‡ǤŠ‡ ’”‘–‡‹Ǧ Šƒ’‡”‘‡ ‘’Ž‡š‹•†‹”‡ –‡†–‘–Š‡‡„”ƒ‡„›–Š‡•‹‰ƒŽ•‡“—‡ ‡ǡ™Š‡”‡ ‹– ‹• ”‡ ‘‰‹•‡† „› –Š‡ ‡ Ǧ ‘’Ž‡š ͳͲ͵ ™Š‹ Š ƒ –• ƒ• ƒ ‡„”ƒ‡ ”‡ ‡’–‘”Ǥ Š‡ ƒ –—ƒŽ –”ƒ•Ž‘ ƒ–‹‘‘ —”••‹‹Žƒ”ƒ•‹–Š‡Ǧ†‡’‡†‡–’ƒ–Š™ƒ›–Š”‘—‰Š–Š‡‡ ͸ͳ’ Šƒ‡ŽǤ

(14) S.cerevisiaeʹͲ‰‡‡•Šƒ˜‡„‡‡‹†‡–‹ˆ‹‡†–‘’Žƒ›ƒ”‘Ž‡‹–Š‡–”ƒ•Ž‘ ƒ–‹‘’”‘ ‡••‘ˆ ‡™Ž›•›–Š‡•‹•‡†’”‘–‡‹•‹–‘–Š‡Ǥ ‡‘‡•‡“—‡ ‹‰‘ˆA.niger‹†‡–‹ˆ‹‡†ͳͺ‰‡‡• –Šƒ– ‡ ‘†‡ ›‡ƒ•– ‘”–Š‘Ž‘‰• ‘ˆ –Š‘•‡ ‰‡‡• ͳʹ͸Ǥ • ‹ ƒƒŽ•ǡ ‘ ‘”–Š‘Ž‘‰ ‘ˆ –Š‡ S. cerevisiae•‹‰ƒŽ”‡ ‘‰‹–‹‘ƒ††‘ ‹‰’”‘–‡‹”’ʹͳ’™ƒ•ˆ‘—†ǡƒ‰‡‡–Šƒ–‹•‡••‡–‹ƒŽ ‹›‡ƒ•–ǤŽ•‘‘Š‘‘Ž‘‰—‡™ƒ•ˆ‘—†ˆ‘”–Š‡‘Ǧ‡••‡–‹ƒŽ›‡ƒ•–SSH1‰‡‡ǡ™Š‹ Š ‘†‡• ˆ‘” –Š‡ ƒŽ’Šƒ •—„—‹– ‘ˆ –Š‡ •Šͳ –”ƒ•Ž‘ ‘ ‘’Ž‡š ‘ˆ –Š‡ Ǥ ‡•’‹–‡ –Š‡ ƒ’’ƒ”‡– ƒ„•‡ ‡‘ˆ–Š‘•‡–™‘‰‡‡•‹A.nigerǡ’”‘–‡‹–”ƒ•Ž‘ ƒ–‹‘‹–‘–Š‡‹•–Š‘—‰Š––‘‘ —” ƒƒŽ‘‰‘—•–‘›‡ƒ•–Ǥ Ž–Š‘—‰Š ’”‘–‡‹• ƒ”‡ –ƒ”‰‡–‡† –‘ –Š‡  „› –Š‡‹” •‹‰ƒŽ •‡“—‡ ‡ǡ –Š‡‹” —Ž–‹ƒ–‡ †‡•–‹ƒ–‹‘ƒ›„‡†‹ˆˆ‡”‡–ǤŠ‡›ƒ›„‡†‡•–‹‡†ˆ‘”•‡ ”‡–‹‘ǡ–ƒ”‰‡–‡†–‘‘–Š‡” ‡ŽŽ—Žƒ” †‡•–‹ƒ–‹‘•‘”Šƒ˜‡–Š‡ƒ•–Š‡‹”ˆ‹ƒŽ†‡•–‹ƒ–‹‘Ǥ”‡•‹†‡–’”‘–‡‹•ƒ”‡”‡–ƒ‹‡†‹ –Š‡ ‘’ƒ”–‡– †—‡ –‘ ƒ Ǧ–‡”‹ƒŽ –‡–”ƒ‡”‹  ȋȀ Ȍ ”‡–‡–‹‘ •‹‰ƒŽ ͳʹ͹ ™Š‹ Š –ƒ”‰‡–•–Š‡’”‘–‡‹„ƒ –‘–Š‡‹ˆ‹–‡†•—’‹–Š‡ ‘Ž‰‹Ǥ   ProteinFoldingintheEndoplasmicReticulum(ER) ˆ–‡”–”ƒ•Ž‘ ƒ–‹‘‹–‘ –Š‡ ǡ –Š‡ •‹‰ƒŽ •‡“—‡ ‡ ‘ˆ–Š‡ ƒ• ‡– ’”‘–‡‹ ‹•”‡‘˜‡† „› –Š‡ •‹‰ƒŽ ’‡’–‹†ƒ•‡ ‘’Ž‡š ͵ͳǡ ƒ† –Š‡ ’”‘–‡‹• —†‡”‰‘ ƒ••‹•–‡† ˆ‘Ž†‹‰ ƒ† †‹•–‹ – ‘†‹ˆ‹ ƒ–‹‘••— Šƒ•†‹•—Žˆ‹†‡„”‹†‰‡ˆ‘”ƒ–‹‘ǡcistrans‹•‘‡”‹•ƒ–‹‘‘ˆ’‡’–‹†‡„‘†• ’”‡ ‡†‹‰’”‘Ž‹‡”‡•‹†—‡•ǡƒ†–Š‡‹‹–‹ƒ–‹‘‘ˆ‰Ž› ‘•›Žƒ–‹‘Ǥ. GeneralIntroduction13.

(15) Chapter1 ”‘–‡‹•‡–‡”–Š‡‹ƒ‹ƒ–—”‡ˆ‘”ƒ†–Š‡”‡ˆ‘”‡†‹•’Žƒ›ƒ ‘•‹†‡”ƒ„Ž‡ƒ‘—–‘ˆ Š›†”‘’Š‘„‹  ƒ”‡ƒ•ǡ ™Š‹ Š ƒ––”ƒ – ‡ƒ Š ‘–Š‡” ‹ –Š‡ ƒ“—‡‘—• ‡˜‹”‘‡– ‘ˆ –Š‡ ǡ ƒ† ‘—Ž†‰‹˜‡”‹•‡–‘’”‘–‡‹ƒ‰‰”‡‰ƒ–‹‘Ǥ‹’‘”–ƒ–ˆ— –‹‘‘ˆ–Š‡‹•–‘’”‡˜‡––Š‡•‡ —™ƒ–‡†‹–‡”ƒ –‹‘•„‡–™‡‡‹ƒ–—”‡’”‘–‡‹•ƒ†–‘‡ƒ„Ž‡‡ˆˆ‹ ‹‡–’”‘–‡‹ˆ‘Ž†‹‰Ǥ Š‹•‹•ƒ••‹•–‡†„›ƒ•‡–‘ˆǦ”‡•‹†‡– Šƒ’‡”‘‡•ƒ†ˆ‘Ž†ƒ•‡•ǤA.niger‡ ‘†‡••‡˜‡–‡‡ Ž—‹ƒŽ ’”‘–‡‹• –Šƒ– ƒ”‡ ‹˜‘Ž˜‡† ‹ –Š‡ ’”‘–‡‹ ˆ‘Ž†‹‰ ’”‘ ‡••‡• ‹ –Š‡  ͳʹ͸Ǥ Š‡› ‹ Ž—†‡ Šƒ’‡”‘‡• Ž‹‡ ‹ ȋ„‹†‹‰ ’”‘–‡‹Ȍ ƒ† ƒŽ‡š‹ǡ ƒ† ˆ‘Ž†ƒ•‡• ‘ˆ –Š‡ ’”‘–‡‹ †‹•—Ž’Š‹†‡‹•‘‡”ƒ•‡ˆƒ‹Ž›ȋ

(16) Ȍƒ†’‡’–‹†›ŽǦ’”‘Ž›Žcistrans‹•‘‡”ƒ•‡ˆƒ‹Ž›ȋ

(17) ȌǤ Š‡’”‘ ‡••‘ˆ’”‘–‡‹ˆ‘Ž†‹‰‹–Š‡‘ˆAspergilliŠƒ•”‡ ‡–Ž›„‡‡”‡˜‹‡™‡†„›. ‡›•‡•etal. ͶͲǤƒ•‡†‘–Š‡ƒƒŽ›•‹•‘ˆ–Š‡‰‡‘‡•‡“—‡ ‡•‘ˆA.nigerƒ†A.nidulans –Š‡›”‡˜‹‡™˜ƒ”‹‘—•ƒ•’‡ –•’”‘–‡‹ˆ‘Ž†‹‰‹–Š‡Ž‹‰Š–‘ˆ‘™Ž‡†‰‡ˆ”‘S.cerevisiaeƒ† PichiapastorisǤ   Chaperones Š‡ Šƒ’‡”‘‡‹‹•ƒ‡„‡”‘ˆ–Š‡Š‡ƒ–•Š‘ ͹Ͳ’”‘–‡‹ˆƒ‹Ž›ȋ •’͹ͲȌǡƒ†‹–‹•‘‡‘ˆ –Š‡ „‡•– •–—†‹‡† Šƒ’‡”‘‡• ˆ‘” ™Š‹ Š ƒ Š‘‘Ž‘‰—‡ ȋbipAȌ Šƒ• „‡‡ Ž‘‡† ‹ A. niger ͳ͵Ͳǡͳ͸ͺǤ‹„‹†•–‘Š›†”‘’Š‘„‹ •–”‡– Š‡•ƒ••‘‘ƒ•–Š‡‰”‘™‹‰’‘Ž›’‡’–‹†‡ Šƒ‹‡–‡”•. –Š‡–‘•—’’”‡••ƒ‰‰”‡‰ƒ–‹‘ǡƒ†‹–’”‘‘–‡•–Š‡–”ƒ•Ž‘ ƒ–‹‘‘ˆ–Š‡’‘Ž›’‡’–‹†‡ Šƒ‹ ƒ ”‘••–Š‡‡„”ƒ‡ͶͳǤŠ‡„‹†‹‰ƒ†–Š‡”‡Ž‡ƒ•‡‘ˆ‹–‘ƒ†ˆ”‘’‡’–‹†‡•‹• ‘—’Ž‡† –‘–Š‡Š›†”‘Ž›•‹•‘ˆȋ ‹‰ǤʹȌǤ‘–‘Ž›‹•‹‹˜‘Ž˜‡†‹„‹†‹‰‹ƒ–—”‡’”‘–‡‹•ƒ† –Š‡”‡„›‹–Š‡“—ƒŽ‹–› ‘–”‘Ž‘ˆ’”‘–‡‹ˆ‘Ž†‹‰ ͳͻͲǡ‹–‹•ƒŽ•‘‹˜‘Ž˜‡†‹”‡‰—Žƒ–‹‰–Š‡ –Š”‘—‰Š‹–•ƒ••‘ ‹ƒ–‹‘™‹–Š–Š‡–”ƒ•‡„”ƒ‡‹ƒ•‡

(18) ”‡Ǥ‹‹•–Š‡”‡ˆ‘”‡”‡‰ƒ”†‡†ƒ•ƒ ‡› ‘Ž‡ —Žƒ” Šƒ’‡”‘‡Ǥ

(19)  ƒ††‹–‹‘ –‘ ‹’ǡ ƒ‘–Š‡” ’—–ƒ–‹˜‡ ͹Ͳ Šƒ’‡”‘‡ǡ •Šǡ ™ƒ• ˆ‘—† ‹ A. nigerǤ

(20)  ›‡ƒ•–ǡ •Šͳ’ ƒ† –Š‡ ‹’ Š‘‘Ž‘‰—‡ ƒ”ʹ’ Šƒ˜‡ ‹–‡”ƒ –‹‘• ™‹–Š ƒ  ’”‘–‡‹•ǡ ‡ ͸͵ ƒ† –Š‡ — Ž‡‘–‹†‡ ‡š Šƒ‰‡ ˆƒ –‘” ‹Žͳ’ ͳͷͷǤ ‹Žͳ’ ‹–‡”ƒ –• †‹”‡ –Ž› ™‹–Š –Š‡ ƒ•‡ †‘ƒ‹ ‘ˆ ƒ”ʹ’ǡ ‘†—Žƒ–‹‰ –Š‡ ƒ –‹˜‹–› ‘ˆ –Š‡ Šƒ’‡”‘‡ ͳ͸͵Ǥ —”’”‹•‹‰Ž›ǡ‘Š‘‘Ž‘‰—‡ˆ‘”‹Žͳ’™ƒ•ˆ‘—†‹A.nigerͳʹ͸Ǥ Š‡‰‡‡‡ ‘†‹‰–Š‡A.niger Šƒ’‡”‘‡ ƒŽ‡š‹ȋclxAȌŠƒ•ƒŽ•‘„‡‡ Ž‘‡†ƒ† Šƒ”ƒ –‡”‹•‡†. ͳ͹ǡͳ͹͵Ǥ. ƒŽ‡š‹ ‹• ƒ Ž‡ –‹ǦŽ‹‡ Šƒ’‡”‘‡ǡ ƒ† ƒ ‡••‡–‹ƒŽ ’ƒ”– ‘ˆ –Š‡. ƒ–—”ƒ–‹‘ ƒ† “—ƒŽ‹–› ‘–”‘Ž ‡ Šƒ‹• ‘ˆ ‰Ž› ‘’”‘–‡‹•Ǥ

(21) – •’‡ ‹ˆ‹ ƒŽŽ› ‹–‡”ƒ –• ™‹–Š ’ƒ”–‹ƒŽŽ› –”‹‡† ‘‘‰Ž— ‘•›Žƒ–‡† ǦŽ‹‡† ‘Ž‹‰‘•ƒ Šƒ”‹†‡•Ǥ

(22) – •‡”˜‡• ƒ• ƒ ƒ”„‘Š›†”ƒ–‡Ǧ„‹†‹‰’”‘–‡‹ƒŽŽ‘™‹‰ˆ‘” › Ž‡•‘ˆ†‡‰Ž— ‘•›Žƒ–‹‘ƒ†”‡‰Ž— ‘•›Žƒ–‹‘‘ˆ –Š‡ƒ–—”‹‰’”‘–‡‹Ǥ. 14GeneralIntroduction.

(23) Chapter1                . Figure2ǤŠ‡‹Ǧ › Ž‡Ǥ ‘†‹ˆ‹‡†ƒˆ–‡” Š”Ú†‡”ƒ†ƒ—ˆƒͳͶͶǤ.     Foldases.

(24)  ƒ††‹–‹‘ –‘ –Š‡ Šƒ’‡”‘‡•ǡ ˆ‘Ž†ƒ•‡• ƒ”‡ ‹˜‘Ž˜‡† ‹ –Š‡ ’”‘–‡‹ ˆ‘Ž†‹‰Ǥ ‘Ž†ƒ•‡• ƒ–ƒŽ›•‡ •Ž‘™ ƒ† ‘ˆ–‡ ”ƒ–‡ Ž‹‹–‹‰ ‘˜ƒŽ‡– Šƒ‰‡• •— Š ƒ• –Š‡ ˆ‘”ƒ–‹‘ ‘ˆ †‹•—Žˆ‹†‡ „‘†• „‡–™‡‡ ›•–‡‹‡ ”‡•‹†—‡•ǡ ƒ† –Š‡ ‹•‘‡”‹•ƒ–‹‘ ‘ˆ ’‡’–‹†‡ „‘†• ’”‡ ‡†‹‰ ’”‘Ž‹‡”‡•‹†—‡•Ǥ Š‡ ‘š‹†‹•‹‰ ‡˜‹”‘‡– ‘ˆ –Š‡  ˆƒ˜‘—”• –Š‡ ˆ‘”ƒ–‹‘ ‘ˆ †‹•—Ž’Š‹†‡ „‘†•ǡ ™Š‹ Šƒ”‡”‡“—‹”‡†ˆ‘”–Š‡•–ƒ„‹Ž‹–›ƒ†ˆ— –‹‘‘ˆƒŽƒ”‰‡—„‡”‘ˆ•‡ ”‡–‡†’”‘–‡‹• ͵ʹǤ Š‡ˆ‘”ƒ–‹‘ƒ†”‡ƒ””ƒ‰‡‡–‘ˆ†‹•—Ž’Š‹†‡„”‹†‰‡•‹• ƒ–ƒŽ›•‡†„›

(25) ǯ• ͳͲͻǤ

(26) ‹•ƒ ’”‘–‡‹ –Š‹‘ŽǦ‘š‹†‘”‡†— –ƒ•‡ –Šƒ– ƒ–ƒŽ›•‡• –Š‡ ‘š‹†ƒ–‹‘ǡ ”‡†— –‹‘ ƒ† ‹•‘‡”‹•ƒ–‹‘ ‘ˆ ’”‘–‡‹ †‹•—Ž’Š‹†‡ „‘†•Ǥ Š‡ ‰‡‡• ‡ ‘†‹‰ –Š‡ A. niger 

(27)  ƒ† •‡˜‡”ƒŽ 

(28) Ǧ”‡Žƒ–‡† ‰‡‡• Šƒ˜‡ „‡‡ ‹•‘Žƒ–‡† ƒ† Šƒ”ƒ –‡”‹•‡†Ǥ Š‡•‡ ƒ”‡ pdiA ͳͲͶ ‡ ‘†‹‰ 

(29) ǡ ƒ† –Š‡ ‰‡‡•tigA ͸ʹƒ†prpA ͳ͹Ͷ‡ ‘†‹‰–Š‡

(30) Ǧ”‡Žƒ–‡†’”‘–‡‹•

(31) ȋ–—‹ ƒ› ‹‹†— ‹„Ž‡ ‰‡‡Ȍ ƒ† ȋ

(32) Ǧ”‡Žƒ–‡† ’”‘–‡‹ȌǤ A. niger ‡ ‘†‡• ƒŽ•‘ ƒ ’—–ƒ–‹˜‡ ‡„”ƒ‡Ǧ„‘—† 

(33) Ǧˆƒ‹Ž›’”‘–‡‹ȋ’•Ȍͳʹ͸Ǥ ”ƒ•ˆ‡” ‘ˆ ‡Ž‡ –”‘• †—”‹‰ ‘š‹†ƒ–‹˜‡ ’”‘–‡‹ ˆ‘Ž†‹‰ǡ ‹ ˆ‘” ‡šƒ’Ž‡ †‹•—Ž’Š‹†‡ „‘† ˆ‘”ƒ–‹‘ǡ ”‡“—‹”‡• ‹ S. cerevisiae –Š‡  ‡„”ƒ‡ ’”‘–‡‹ ”‘ͳ’ ȋ ‹‰Ǥ ͵Ȍ ͵͸ǡͳ͸ʹǤ ‘‘Ž‘‰—‡•‘ˆ–Š‹•’”‘–‡‹Šƒ˜‡ƒŽ•‘„‡‡†‹• ‘˜‡”‡†‹–Š‡Aspergillus‰‡‘‡•ͳʹ͸Ǥ. GeneralIntroduction15.

(34) Chapter1                 . Figure3Ǥš‹†ƒ–‹˜‡’”‘–‡‹ˆ‘Ž†‹‰‡†‹ƒ–‡†„›

(35) Ǥ.   . Š‡ 

(36) ƒ•‡• ƒ–ƒŽ›•‡ –Š‡ cistrans ‹•‘‡”‹•ƒ–‹‘ ‘ˆ ’‡’–‹†‡ „‘†• ’”‡ ‡†‹‰ ’”‘Ž‹‡ ”‡•‹†—‡•ȋ ‹‰ǤͶȌǤ ‘”‡˜‡”›ƒ‹‘ƒ ‹†”‡•‹†—‡‡š ‡’–ˆ‘”’”‘Ž‹‡ǡ–Š‡”‡‹••–‡”‹ Š‹†”ƒ ‡ „‡–™‡‡ –Š‡ ‡‹‰Š„‘—”‹‰ •‹†‡ Šƒ‹• ˆ‘” –Š‡ cis ‘ˆ‘”ƒ–‹‘ „—– ‘– ˆ‘” –Š‡ trans ‘ˆ‘”ƒ–‹‘ǤŠ‡’‡’–‹†‡„‘†•ˆ‘”–Š‡•‡”‡•‹†—‡•ƒ”‡–Š‡”‡ˆ‘”‡ƒŽŽtransǤ ‘™‡˜‡”ǡ‹–Š‡ ƒ•‡‘ˆ’”‘Ž‹‡–Š‡•–‡”‹ Š‹†”ƒ ‡‹•ƒŽ‘•–‡“—ƒŽˆ‘”„‘–Š‹•‘‡”•ǡŠ‡ ‡–Š‡’”‡•‡ ‡‘ˆ 

(37) ƒ•‡•Ǥ

(38) ƒ–‹˜‡’”‘–‡‹•‘”‡–ŠƒͳͲΨ‘ˆ–Š‡’”‘Ž‹‡’‡’–‹†‡„‘†• ƒ„‡‹–Š‡cis ‘ˆ‘”ƒ–‹‘. ͺ͸Ǥ. Š‡ 

(39) ƒ•‡• ™‡”‡ †‹• ‘˜‡”‡† †—‡ –‘ –Š‡‹” ƒ„‹Ž‹–› –‘ „‹† –‘. ‹—‘•—’’”‡••‹˜‡ †”—‰•Ǥ

(40)  ˆ‹Žƒ‡–‘—• ˆ—‰‹ –™‘ ƒŒ‘” Žƒ••‡• ‘ˆ 

(41) ƒ•‡• Šƒ˜‡ „‡‡ †‹• ‘˜‡”‡†Ǣ Š‡ › Ž‘’Š‹Ž‹• ™Š‹ Š „‹† –‘ › Ž‘•’‘”‹  ȋ•Ȍǡ ƒ† –Š‡ ͷͲ͸ „‹†‹‰ ’”‘–‡‹•ȋ •Ȍ™Š‹ Š ƒ„‹†–‘–Š‡ ͷͲ͸ ‘’‘—†•Ǥ ‘™‡˜‡”ǡ‘•–‘ˆ–Š‡

(42) ƒ•‡• ’”‡†‹ –‡†ˆ”‘–Š‡ˆ—‰ƒŽ‰‡‘‡•ƒ”‡ ›–‘•‘Ž‹ ǡƒ†‘Ž›ˆ‡™”‡•‹†‡–‘‡•Šƒ˜‡„‡‡ ‹†‡–‹ˆ‹‡†Ž‹‡–Š‡cypB‰‡‡‘ˆA.niger™Š‹ Š‡ ‘†‡•ƒ”‡•‹†‡– › Ž‘’Š‹Ž‹ǦŽ‹‡

(43)  ʹ͹Ǥ.

(44) –• Ǧ–‡”‹ƒŽ   ”‡–‡–‹‘ •‹‰ƒŽ ‹• •‘‡™Šƒ– †‹˜‡”‰‡– ˆ”‘ –Š‡ Ȁ . ‘•‡•—•ǡ „—– ‡š’‡”‹‡–ƒŽ †ƒ–ƒ ’”‘˜‡† ‹–•  Ž‘ ƒŽ‹•ƒ–‹‘Ǥ Š‡ ’—–ƒ–‹˜‡ A. niger  Ž—‡ƒŽ ’”‘–‡‹ ”‘ ƒŽ•‘ Šƒ• ƒ ’”‡†‹ –‡† Ǧ–‡”‹ƒŽ  Ǧ”‡–‡–‹‘ •‹‰ƒŽ ͳʹ͸Ǥ Š‡ ‰‡‘‡ •‡“—‡ ‡ ‘ˆ A. niger ƒŽ•‘ ”‡˜‡ƒŽ‡† ƒ ‰‡‡ ˆ‘” ƒ •‡ ‘† ǦŽ‘ ƒŽ‹•‡† 

(45) ƒ•‡ǡ ƒ Ǧ–›’‡’‡’–‹†›ŽǦ’”‘Ž›Žcistrans‹•‘‡”ƒ•‡ȋͲͳ‰Ͳ͸͸͹ͲȌǤ. 16GeneralIntroduction.

(46) Chapter1            Figure4Ǥ

(47) •‘‡”‹•ƒ–‹‘‘ˆ’‡’–‹†‡„‘†•’”‡ ‡†‹‰’”‘Ž‹‡”‡•‹†—‡•ǡ ƒ–ƒŽ›œ‡†„›

(48) ƒ•‡•Ǥ.   Glycosylation Š‡ ƒŒ‘”‹–› ‘ˆ ’”‘–‡‹• •‡ ”‡–‡† „› ˆ‹Žƒ‡–‘—• ˆ—‰‹ ƒ”‡ ‰Ž› ‘•›Žƒ–‡†ǡ ƒ ’”‘ ‡•• –Šƒ– •–ƒ”–•‹–Š‡ǤŽ‹‰‘•ƒ Šƒ”‹†‡‘‹‡–‹‡•ƒ”‡‡‹–Š‡”ƒ––ƒ Š‡†–‘ƒ•’ƒ”ƒ‰‹‡”‡•‹†—‡•‹Ǧ Ž‹‡†‰Ž› ‘•›Žƒ–‹‘‘”–‘•‡”‹‡‘”–Š”‡‘‹‡”‡•‹†—‡•‹ǦŽ‹‡†‰Ž› ‘•›Žƒ–‹‘ǤǦŽ‹‡† ‰Ž› ‘•›Žƒ–‹‘ ‘ˆ ’”‘–‡‹•ǡ ‹• „‡•– —†‡”•–‘‘†ǡ ƒ† •‡”˜‡• Š‹‰ŠŽ› †‹˜‡”•‡ ˆ— –‹‘•Ǥ

(49) – •–ƒ„‹Ž‹•‡•–Š‡’”‘–‡‹•ƒ‰ƒ‹•–†‡ƒ–—”ƒ–‹‘ƒ†’”‘–‡‘Ž›•‹•ǡ‡Šƒ ‡••‘Ž—„‹Ž‹–›ǡ‘†—Žƒ–‡• ‹—‡ ”‡•’‘•‡•ǡ ˆƒ ‹Ž‹–ƒ–‡• ‘”‹‡–ƒ–‹‘ ‘ˆ ’”‘–‡‹• ”‡Žƒ–‹˜‡ –‘ ƒ ‡„”ƒ‡ǡ ‘ˆ‡”• •–”— –—”ƒŽ ”‹‰‹†‹–› –‘ ’”‘–‡‹•ǡ ”‡‰—Žƒ–‡• ’”‘–‡‹ –—”‘˜‡”ǡ ƒ† ˆ‹‡Ǧ–—‡• –Š‡ Šƒ”‰‡ ƒ† ‹•‘‡Ž‡ –”‹ ’‘‹–‘ˆ’”‘–‡‹•ͷͷǤ. Ž› ‘•›Žƒ–‹‘ƒŽ•‘’Žƒ›•ƒ‹’‘”–ƒ–”‘Ž‡‹–Š‡“—ƒŽ‹–› ‘–”‘Ž‡ Šƒ‹•‘ˆ–Š‡  ʹͺǡƒ•‹–†‹•–‹‰—‹•Š‡•—ˆ‘Ž†‡†ˆ”‘ˆ‘Ž†‡†ƒ†‹•ˆ‘Ž†‡†’”‘–‡‹•Ǥ Ž› ‘•›Žƒ–‹‘•–ƒ”–• ‘–Š‡ƒ• ‡–’‘Ž›’‡’–‹†‡ Šƒ‹ƒ•‹–‡–‡”•–Š‡ǤŠ‡‘Ž‹‰‘•ƒ Šƒ”›Ž–”ƒ•ˆ‡”ƒ•‡ǡ™Š‹ Š ‹•ƒ••‘ ‹ƒ–‡†™‹–Š–Š‡–”ƒ•Ž‘ ‘ǡ• ƒ•ƒ†‰Ž› ‘•›Žƒ–‡•ƒ•’ƒ”ƒ‰‹‡”‡•‹†—‡•‹–Š‡•‡“—‘ ǦǦȀǡ™Š‡”‡‹•ƒ›ƒ‹‘ƒ ‹†‡š ‡’–’”‘Ž‹‡ ͷͷǤŠ‡‘Ž‹‰‘•ƒ Šƒ”›ŽǦ–”ƒ•ˆ‡”ƒ•‡ƒ††• ǦŽ‹‡† ‘Ž‹‰‘•ƒ Šƒ”‹†‡• –‘ –Š‡ •‹†‡ Šƒ‹ ‹–”‘‰‡ ‘ˆ –Š‡ ƒ•’ƒ”ƒ‰‹‡ ”‡•‹†—‡ „› ƒ Ǧ ‰Ž› ‘•‹†‹  „‘†Ǥ Š‡ ǦŽ‹‡† ‰Ž› ƒ ‘”‡ ‹ ˆ—‰‹ Šƒ• •Š‘™ –‘ „‡ ‹†‡–‹ ƒŽ –‘ –Š‡ ƒƒŽ‹ƒǦŽ‹‡† ‘”‡ȋ Ž ͵ƒͻ Ž ƒ ʹȌͺͺǤˆ–‡”–Š‡‹‹–‹ƒŽ‰Ž› ‘•›Žƒ–‹‘ǡ‰Ž— ‘•‹†ƒ•‡

(50)  ƒ† ‰Ž— ‘•‹†ƒ•‡

(51)

(52)  –”‹ –Š‡ ‘Ž‹‰‘•ƒ Šƒ”‹†‡ –‘ –Š‡ ‘‘‰Ž— ‘•›Žƒ–‡† ˆ‘” ȋ Ž ͳƒͻ Ž ƒ ʹȌǡ ™Š‹ Š ƒŽŽ‘™• –Š‡ ‰Ž› ‘’‡’–‹†‡• –‘ ‹–‡”ƒ – ™‹–Š ƒŽ‡š‹ ƒ† ƒŽ”‡–‹ —Ž‹ ͶͻǤƒŽ”‡–‹ —Ž‹‹•–Š‡•‘Ž—„Ž‡ ‘—–‡”’ƒ”–‘ˆ ƒŽ‡š‹ǤƒŽ”‡–‹ —Ž‹‹•’”‡•‡–‹ ƒƒŽ‹ƒ ‡ŽŽ•ǡ„—–‘–‹›‡ƒ•–ƒ†A.nigerǤ‡‹‰ƒŽ‡ –‹ǡ ƒŽ‡š‹•’‡ ‹ˆ‹ ƒŽŽ›‹–‡”ƒ –• ™‹–Š‰Ž› ‘’”‘–‡‹•ǡ„—–‘Ž›‹ˆ–Š‡›Šƒ˜‡‘‘‰Ž— ‘•›Žƒ–‡†Ǧ‰Ž› ƒ•Ǥ

(53) ƒƒŽ‹ƒ ‡ŽŽ•ǡ ‹– Šƒ• „‡‡ •Š‘™ –Šƒ– ƒ –Š‹‘”‡†‘š‹ ˆƒ‹Ž› ˆ‘Ž†ƒ•‡ ȋ”’ͷ͹Ȍ ƒ••‘ ‹ƒ–‡• ™‹–Š –Š‡ ƒŽ‡š‹ ƒ†’”‘‘–‡•ˆ‘Ž†‹‰ ͷ͹Ǥ‡‘˜ƒŽ‘ˆ–Š‡”‡ƒ‹‹‰‰Ž— ‘•‡ˆ”‘–Š‡‰Ž› ƒ„›‰Ž— ‘•‹†ƒ•‡ GeneralIntroduction17.

(54) Chapter1

(55)

(56)  ”‡•—Ž–• ‹ –Š‡ †‹••‘ ‹ƒ–‹‘ ‘ˆ –Š‡ ‰Ž› ‘’‡’–‹†‡• ˆ”‘ ƒŽ‡š‹Ǥ

(57) ˆǡ ƒ– –Š‹• ’‘‹–ǡ –Š‡ ‰Ž› ‘’”‘–‡‹ ‹• ˆ‘Ž†‡† ‘””‡ –Ž›ǡ ‹– ™‹ŽŽ „‡ ‘ Ž‘‰‡” ”‡–ƒ‹‡† ‹ –Š‡  ƒ† ™‹ŽŽ „‡ –”ƒ•’‘”–‡† –‘ –Š‡ ‘Ž‰‹ ‘’Ž‡šǤ

(58) ˆ ‘–ǡ ”‡Ǧƒ††‹–‹‘ ‘ˆ ƒ ‰Ž— ‘•‡ ”‡•‹†—‡ –‘ –Š‡ ǦŽ‹‡† ‰Ž› ƒ‘ —”•„›–Š‡ƒ –‹‘‘ˆ–Š‡‰Ž— ‘•‡ǣ‰Ž› ‘’”‘–‡‹‰Ž— ‘•›Ž–”ƒ•ˆ‡”ƒ•‡ȋ. Ȍǡƒ Ž—‹ƒŽ ‡œ›‡ –Šƒ– ƒ –• ƒ• ƒ ˆ‘Ž†‹‰ •‡•‘” ͳ͵ͶǤ Š‹• ˆ‘Ž†‹‰ •‡•‘” ƒ‡• —’ –Š‡  “—ƒŽ‹–› ‘–”‘ŽȋȌ•›•–‡–‘‰‡–Š‡”™‹–Š–Š‡Ž‡ –‹•ǤŠ‡”‡‰Ž— ‘•›Žƒ–‹‘„›. –ƒ‰• –Š‡‹ ‘’Ž‡–‡ˆ‘Ž†‡†‰Ž› ‘’”‘–‡‹ˆ‘””‡‡™‡†‹–‡”ƒ –‹‘™‹–Š ƒŽ‡š‹ǡƒ†–Š‡”‡ˆ‘”‡ƒ ‡™ ˆ‘Ž†‹‰ ƒ––‡’–Ǥ Š‡ †‡‰Ž— ‘•›Žƒ–‹‘Ǧ”‡‰Ž— ‘•›Žƒ–‹‘ › Ž‡ ‘–‹—‡• —–‹Ž ’”‘’‡” ˆ‘Ž†‹‰‹•ƒ Š‹‡˜‡†ȋ ‹‰ǤͷȌǤŠ‡ƒ‹ˆ‡ƒ–—”‡•‘ˆ–Š‡ › Ž‡ƒ”‡™‡ŽŽ‡•–ƒ„Ž‹•Š‡†ǡƒ††‡–ƒ‹Ž‡† ƒ•’‡ –• ƒ”‡ ”‡˜‹‡™‡† ‹ ƒ —„‡” ‘ˆ ’ƒ’‡”• ʹͺǡʹͻǡ͵ͲǡͳʹͳǤ ‘‘Ž‘‰—‡• ™‡”‡ ‹†‡–‹ˆ‹‡† ˆ‘” ‡ƒ”Ž› ƒŽŽ ‘’‘‡–• ‘ˆ –Š‡ ‰Ž› ‘•›Žƒ–‹‘ ’ƒ–Š™ƒ› ƒ† A. niger –Š‡”‡ˆ‘”‡ ’‘–‡–‹ƒŽŽ› ’‘••‡••‡•ƒ™‡ŽŽǦ†‡˜‡Ž‘’‡†‰Ž› ‘•›Žƒ–‹‘Ǧ†‡’‡†‡–“—ƒŽ‹–› ‘–”‘Ž•›•–‡ͳʹ͸Ǥ. Figure5Ǥ“—ƒŽ‹–› ‘–”‘Ž‡ Šƒ‹••ǤŠ‡ ƒŽ‡š‹Ȁ ƒŽ”‡–‹ —Ž‹ › Ž‡Ǥœ›ƒ–‹ ƒ –‹‘•ƒ”‡ ”‡’”‡•‡–‡†‹•“—ƒ”‡„‘š‡•Ǥ„„”‡˜‹ƒ–‹‘•ǣǡ ƒŽ‡š‹Ǣǡ†‡‰”ƒ†ƒ–‹‘Ǧ‡Šƒ ‹‰ȽǦ ƒ‘•‹†ƒ•‡ǦŽ‹‡ ’”‘–‡‹Ǣ ǡ ‰Ž— ‘•‡Ǣ ǡ ƒ‘•‡Ǣ ƒ† . ǡ —”‹†‹‡ †‹’Š‘•’Šƒ–‡ ȋȌǦ ‰Ž— ‘•‡ǣ‰Ž› ‘’”‘–‡‹‰Ž— ‘•›Ž–”ƒ•ˆ‡”ƒ•‡Ǥ‘†‹ˆ‹‡†ƒˆ–‡” Š”Ú†‡”ƒ†ƒ—ˆƒͳͶͶǤ. 18GeneralIntroduction.

(59) Chapter1 TransporttoGolgi Š‡ˆ‘Ž†‡† ‘””‡ –Ž›ǡ–Š‡’”‘–‡‹•’ƒ••–Š‡“—ƒŽ‹–› ‘–”‘Ž•›•–‡‹–Š‡ƒ†ƒ”‡•‡† ‘ˆˆ –‘ –Š‡ ‘Ž‰‹ǦŽ‹‡ •–”— –—”‡ ™Š‡”‡ –Š‡› ƒ —†‡”‰‘ ˆ—”–Š‡” ‘†‹ˆ‹ ƒ–‹‘• •— Š ƒ• Ǧ Ž‹‡† ‰Ž› ‘•›Žƒ–‹‘ǡ ’”‘ ‡••‹‰ ‘ˆ ǦŽ‹‡† ‘Ž‹‰‘•ƒ Šƒ”‹†‡•ǡ ’Š‘•’Š‘”›Žƒ–‹‘ ƒ† ’”‘–‡‘Ž›–‹  ’”‘ ‡••‹‰Ǥ Ž–Š‘—‰Š ƒ Žƒ••‹ ƒŽ ‘Ž‰‹Ǧƒ’’ƒ”ƒ–—• ‘•‹•–‹‰ ‘ˆ ƒ •‡”‹‡• ‘ˆ ˆŽƒ––‡‡† ‹•–‡”ƒ‡ ‹• ‘– ‘‘Ž› •‡‡ ‹ ˆ‹Žƒ‡–‘—• ˆ—‰‹ǡ ˆ— –‹‘• ƒ••‘ ‹ƒ–‡† ™‹–Š –Š‡ ‘Ž‰‹ƒ”‡’”‡•‡–ǡƒ†–Š‡–‡” ‘Ž‰‹ǦŽ‹‡•–”— –—”‡‹•‘”ƒŽŽ›—•‡†Ǥ Š‡ –”ƒ•’‘”– ‘ˆ ’”‘–‡‹• „‡–™‡‡ –Š‡  ƒ† –Š‡ ‘Ž‰‹ ‘’Ž‡šǡ ™Š‹ Š ‹• „‹†‹”‡ –‹‘ƒŽǡ‹• ƒ””‹‡†‘—–„›•’‡ ‹ˆ‹ ˜‡•‹ Ž‡•ǤŠ‡”‡ƒ”‡–™‘–›’‡•‘ˆ˜‡•‹ Ž‡•‹˜‘Ž˜‡†‹ –Š‡–”ƒ•’‘”–„‡–™‡‡ƒ† ‘Ž‰‹Ǥ

(60)

(61) ˜‡•‹ Ž‡•ȋ‘ƒ–”‘–‡‹ ‘’Ž‡š

(62)

(63) Ȍƒ”‡‹˜‘Ž˜‡† ‹ –Š‡ ƒ–‡”‘‰”ƒ†‡ –”ƒ•’‘”– ˆ”‘  –‘ ‘Ž‰‹ ͸ǡ ™Š‡”‡ƒ• 

(64)  ˜‡•‹ Ž‡• ƒ”‡ ‹˜‘Ž˜‡† ‹ ”‡–”‘‰”ƒ†‡–”ƒ•’‘”–ʹͲǤ   COPII Š‡ˆ‘”ƒ–‹‘‘ˆ˜‡•‹ Ž‡•ˆ”‘–Š‡•–ƒ”–•™‹–Š–Š‡”‡ ”—‹–‹‰‘ˆ

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(66) ’”‘–‡‹•–‘–Š‡ ‡„”ƒ‡ͺʹǤ

(67) ›‡ƒ•––Š‹•‹•‹‹–‹ƒ–‡†„›–Š‡Ǧ”‡•‹†‡–’”‘–‡‹‡ ͳʹ’ǡ™Š‹ Š•‡”˜‡•ƒ•ƒ ‰—ƒ‹‡— Ž‡‘–‹†‡‡š Šƒ‰‡ˆƒ –‘”ˆ‘”–Š‡•ƒŽŽ ƒ•‡ƒ”ͳ’Ǥƒ”ͳ’‹•ƒ –‹˜‡‹‹–• Ǧ „‘—†ˆ‘”ƒ†”‡ ”—‹–•–Š‡‡ ʹ͵Ǧ‡ ʹͶŠ‡–‡”‘†‹‡”–‘–Š‡‡„”ƒ‡ǤŠ‡ ‘’Ž‡š –Š‡”‡ ”—‹–•–Š‡‡ ͳ͵Ǧ‡ ͵ͳ ‘’Ž‡š™Š‹ Š‹•–Š‘—‰Š––‘’‘Ž›‡”‹•‡–Š‡ ‘ƒ–ƒ††”‹˜‡ –Š‡‡„”ƒ‡†‡ˆ‘”ƒ–‹‘–‘ˆ‘”ƒ

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(69) ˜‡•‹ Ž‡ ͳͶʹǤŠ‡ˆ‘”‹‰˜‡•‹ Ž‡—•–•‘‡Š‘™ ƒ’–—”‡‹–•’”‘–‡‹ ƒ”‰‘Ǥ ‘™–Š‹•‹•ƒ Š‹‡˜‡†‹•‘–›‡–ˆ—ŽŽ›—†‡”•–‘‘†ǡ„—––Š‡ƒ”ͳ’Ǧ ‡ ʹ͵Ǧ‡ ʹͶ ‘’Ž‡š‹•–Š‘—‰Š––‘‹–‡”ƒ –™‹–Š ƒ”‰‘’”‘–‡‹•˜‹ƒ•’‡ ‹ˆ‹ •‘”–‹‰•‹‰ƒŽ•Ǥ —‹˜‡”•ƒŽ‡š’‘”–•‹‰ƒŽŠƒ•‘–„‡‡†‡• ”‹„‡†ǡ‹•–‡ƒ†ƒ—„‡”‘ˆ†‹ˆˆ‡”‡–•‹‰ƒŽ• •‡‡–‘‰‘˜‡”–Š‡‹–‡”ƒ –‹‘™‹–Š–Š‡

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(71) ˜‡•‹ Ž‡ ‘ƒ–Ǥ’‡ ‹ˆ‹ –”ƒ•‡„”ƒ‡ ƒ”‰‘ ’”‘–‡‹• ƒ”‡ •‘”–‡† ‹–‘ –Š‡ 

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(73)  ‘ƒ–‡† ˜‡•‹ Ž‡ „› ‘•‡”˜‡† †‹Ǧƒ ‹†‹  ‘–‹ˆ• ƒ† †‹Ǧ Š›†”‘’Š‘„‹  ‘” ƒ”‘ƒ–‹  ‘–‹ˆ•Ǥ Š‡ •‹‰ƒŽŽ‹‰ ‘–‹ˆ• ‘ˆ –Š‡•‡ –”ƒ•‡„”ƒ‡ ƒ”‰‘ ’”‘–‡‹•ƒ”‡ ›–‘’Žƒ•‹ ƒŽŽ›‡š’‘•‡†ƒ†”‡ ‘‰‹•‡†„›•—„—‹–•‘ˆ–Š‡

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(75)  ‘ƒ– ͷǤŠ‡ •‘”–‹‰ ‘ˆ •‘Ž—„Ž‡ ƒ”‰‘ ’”‘–‡‹• ˆ”‘ –Š‡  ‹• Ž‡•• ™‡ŽŽ Šƒ”ƒ –‡”‹•‡†ǡ „—– –Š‡”‡ ‹• ‡˜‹†‡ ‡ ˆ‘” „‘–Š „—ŽǦˆŽ‘™ ƒ† ”‡ ‡’–‘” ‡†‹ƒ–‡† •‘”–‹‰Ǥ Š‡ ”˜ʹͻ’ –”ƒ•‡„”ƒ‡ ’”‘–‡‹ ˆ”‘ ›‡ƒ•– ‹• ”‡•’‘•‹„Ž‡ ˆ‘” ’ƒ ƒ‰‹‰ ‰Ž› ‘•›Žƒ–‡† ’”‘ǦƒŽ’ŠƒǦˆƒ –‘” ‹–‘ 

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(77)  ˜‡•‹ Ž‡•͹Ǥ

(78) ƒ††‹–‹‘ǡ”˜ʹͻ’‹•ƒŽ•‘Ž‹‡Ž›–‘•‘”–‘–Š‡”•‘Ž—„Ž‡’”‘–‡‹•‹ Ž—†‹‰˜ƒ —‘Žƒ” Š›†”‘Žƒ•‡•ǡ ƒ”„‘š›’‡’–‹†ƒ•‡ ǡ ƒ† ’”‘–‡‹ƒ•‡ Ǥ ‘™‡˜‡”ǡ †‡Ž‡–‹‘ ‘ˆ ERV29 •—‰‰‡•–‡† –Šƒ–ƒ††‹–‹‘ƒŽ ƒ”‰‘Ž‘ƒ†‹‰”‡ ‡’–‘”•—•–„‡’”‡•‡–ǡ•‹ ‡ƒ—„‡”‘ˆ‘–Š‡”•‡ ”‡–‘”› ’”‘–‡‹ ™‡”‡ ’ƒ ƒ‰‡† ‘”ƒŽŽ› ‹ ”˜ʹͻ’ †‡’Ž‡–‡† ‡ŽŽ• ͳͳǤ ˆ–‡” ‘’Ž‡–‹‘ǡ 

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(80)  ˜‡•‹ Ž‡•–”ƒ˜‡Ž‘‹ ”‘–—„—Ž‡•–‘–Š‡cisǦ ‘Ž‰‹ǡ™Š‡”‡–Š‡›ˆ—•‡™‹–Š–Š‡ ‘Ž‰‹‡„”ƒ‡ ƒ† †‡’‘•‹– –Š‡‹” Ž‘ƒ† ‹–‘ –Š‡ ‘Ž‰‹Ǥ —•‹‘ ‘ˆ –Š‡ 

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(82)  ˜‡•‹ Ž‡ ™‹–Š –Š‡ ‘Ž‰‹ ”‡“—‹”‡• †‹•ƒ••‡„Ž›‘ˆ–Š‡ ‘ƒ–ǡ™Š‹ Š‹•‡†‹ƒ–‡†„› Š›†”‘Ž›•‹•‘ƒ”ͳ’ǡ ƒ–ƒŽ›•‡†„›‡ ʹ͵ ͳͳͶǤŠ‡‡ Šƒ‹•„›™Š‹ Š–Š‡–”ƒ•’‘”–”‡ ‡’–‘”•”‡Ž‡ƒ•‡–Š‡‹” ƒ”‰‘—’‘ˆ—•‹‘™‹–Š. GeneralIntroduction19.

(83) Chapter1 –Š‡ ‘Ž‰‹ ‹• ‘– ƒŽŽ Ž‡ƒ” ›‡–ǡ „—– ƒ› ”‡Ž› ‘ ƒ Šƒ‰‡ ‹ ’  ‘” ƒ‘–Š‡” ’Š›•‹‘Ž‘‰‹ ƒŽ ‘†‹–‹‘™Š‹ Š–”‹‰‰‡”•–Š‡†‹••‘ ‹ƒ–‹‘‘ˆ–Š‡ ƒ”‰‘ƒ†‹–•”‡ ‡’–‘”Ǥ   COPI 

(84)  ˜‡•‹ Ž‡• ƒ”‡ ‹˜‘Ž˜‡† ‹ –Š‡ ”‡–”‘‰”ƒ†‡ –”ƒ•’‘”– ˆ”‘ ‘Ž‰‹ –‘ ǡ ƒ† •Š—––Ž‡ ‹•Ž‘ ƒ–‡†Ǧ”‡•‹†‡–’”‘–‡‹•„ƒ –‘–Š‡Ǥƒ”‹‘—•Ǧ”‡•‹†‡––›’‡

(85) –”ƒ•‡„”ƒ‡ ’”‘–‡‹• ‘–ƒ‹ƒ ƒ‘‹ ƒŽ”‡–”‹‡˜ƒŽ‘–‹ˆǡǡ‘–Š‡‹” ›–‘’Žƒ•‹ †‘ƒ‹ ͳͻǤŠ‹• ‘–‹ˆ‹–‡”ƒ –•™‹–Š

(86)  ‘ƒ––‘–”ƒ•’‘”––Š‡’”‘–‡‹•„ƒ –‘–Š‡Ǥ‘Ž—„Ž‡Ǧ”‡•‹†‡– ’”‘–‡‹•„‡ƒ”ƒǦ–‡”‹ƒŽȀ ”‡–‡–‹‘‘””‡–”‹‡˜ƒŽ•‹‰ƒŽ–Šƒ–‡†‹ƒ–‡•‹–‡”ƒ –‹‘ ™‹–Š–Š‡Ȁ ”‡ ‡’–‘”ǡ‹›‡ƒ•–‡ ‘†‡†„›ERD2ǤŽ–Š‘—‰Š–Š‡Ȁ ”‡ ‡’–‘”†‘‡• ‘–’‘••‡••ƒ ƒ‘‹ ƒŽ ›–‘’Žƒ•‹ †‹ǦŽ›•‹‡”‡–”‹‡˜ƒŽ‘–‹ˆǡ ‹–‹•–Š‘—‰Š––‘ƒŽ•‘‹–‡”ƒ – ™‹–Š–Š‡

(87)  ‘ƒ––‘ˆƒ ‹Ž‹–ƒ–‡‹–•–”ƒ•’‘”–„ƒ –‘–Š‡ ͳͲǤŠ‡’”‡ ‹•‡‡ Šƒ‹•„› ™Š‹ Š–Š‡”‡ ‡’–‘”„‹†•‹–•Ž‹‰ƒ†‹•‘–‘™ǡ„—–Ž‹‰ƒ†„‹†‹‰‹•–Š‘—‰Š––‘–”‹‰‰‡” —’–ƒ‡‘ˆ–Š‡ƒ••‡„Ž‡† ‘’Ž‡š‹–‘

(88) ˜‡•‹ Ž‡•ͺ͵Ǥ Š‡ ‘Ž‰‹ ‹• ƒŽ•‘ ‹’‘”–ƒ– ˆ‘” •‘”–‹‰ ’”‘–‡‹• –‘ –Š‡‹” ˆ‹ƒŽ †‡•–‹ƒ–‹‘• Ž‹‡ ˜ƒ —‘Ž‡• ‘” –Š‡ ‡š–‡”ƒŽ ‡˜‹”‘‡–Ǥ ”‘–‡‹• ‡–‡” –Š‡ ‘Ž‰‹ ‘ –Š‡ cisǦ•‹†‡ ƒ† ƒ”‡ –”ƒ•’‘”–‡† –‘ –Š‡ ‡†‹ƒŽ ƒ† transǦ ‘Ž‰‹ „› ˜‡•‹ Ž‡•ǡ ƒ† —†‡”‰‘ ‘†‹ˆ‹ ƒ–‹‘• ‡ƒ™Š‹Ž‡Ǥ

(89)  –Š‡ transǦ ‘Ž‰‹ ‡–™‘” ȋ Ȍ ’”‘–‡‹• ƒ”‡ ˆ‹ƒŽŽ› •‘”–‡† –‘ –Š‡‹” †‡•–‹ƒ–‹‘ǤŠ‡›ƒ”‡‡‹–Š‡”–”ƒ•’‘”–‡†‹˜‡•‹ Ž‡•–‘–Š‡’Žƒ•ƒ‡„”ƒ‡ǡ™Š‡”‡–Š‡› ˆ—•‡ƒ††‡Ž‹˜‡”–Š‡‹” ƒ”‰‘„›‡š‘ ›–‘•‹•ǡ‘”–Š‡›ƒ”‡–”ƒ•’‘”–‡†–‘˜ƒ —‘Ž‡•Ǥš‘ ›–‘•‹• ƒŽ•‘ ‡†‹ƒ–‡• –Š‡ ƒ††‹–‹‘ ‘ˆ Ž‹’‹†• ƒ† ‡„”ƒ‡ ’”‘–‡‹• –‘ –Š‡ ’Žƒ•ƒ ‡„”ƒ‡Ǥ ‘‡ ‘ˆ –Š‡ •‡ ”‡–‡†’”‘–‡‹• ƒ”‡ ”‡“—‹”‡†ˆ‘” ‡ŽŽ ™ƒŽŽ „‹‘•›–Š‡•‹•ǡ ™Š‡”‡ƒ• ‘–Š‡”• ƒ”‡ †‡†‹ ƒ–‡†–‘–Š‡Š›†”‘Ž›•‹•‘ˆ’‘Ž›‡”‹ •—„•–”ƒ–‡•ƒ†ƒ”‡”‡Ž‡ƒ•‡†‹–‘–Š‡•—””‘—†‹‰•Ǥ   ERStressResponses Š‡•‡ ”‡–‘”›’ƒ–Š™ƒ›‹•–Š—•”‡•’‘•‹„Ž‡ˆ‘”–Š‡’”‘†— –‹‘ƒ†–”ƒ•’‘”–‘ˆ‡„”ƒ‡ ƒ† •‡ ”‡–‘”› ’”‘–‡‹• ƒ† ’”‘–‡‹• ™‹–Š ‘–Š‡” ‡ŽŽ—Žƒ” †‡•–‹ƒ–‹‘• Ž‹‡ ‡†‘•‘‡• ƒ† Ž›•‘•‘‡•ǤŠ‡’Žƒ›•ƒ’‹˜‘–ƒŽ”‘Ž‡‹–Š‡’”‘†— –‹‘ƒ†ƒ••‡„Ž›ǦŽ‹‡‘ˆ–Š‡•‡ ”‡–‘”› ’ƒ–Š™ƒ›ǡ ƒ• ‹– ‡š‡ —–‡• •‘‡ ƒŒ‘” ’Š›•‹‘Ž‘‰‹ ƒŽ ˆ— –‹‘•Ǥ ‘– ‘Ž› ƒ”‡ ’”‘–‡‹• •›–Š‡•‹•‡†ƒ––Š‡ǡ–Š‡ƒŒ‘”‹–›‘ˆ–Š‡’”‘–‡‹•ƒŽ•‘ˆ‘Ž†‹–‘–Š‡‹”ƒ–‹˜‡ ‘ˆ‘”ƒ–‹‘ ‹ –Š‡ Ǥ – –Š‡ •ƒ‡ –‹‡ –Š‡•‡ ƒ• ‡– ’”‘–‡‹• —†‡”‰‘ ƒ •‡”‹‡• ‘ˆ ’‘•–Ǧ–”ƒ•Žƒ–‹‘ƒŽ ‘†‹ˆ‹ ƒ–‹‘•ǡ •— Š ƒ• †‹•—Ž’Š‹†‡ „‘† ˆ‘”ƒ–‹‘ ƒ† –Š‡ ƒ††‹–‹‘ ‘ˆ ǦŽ‹‡† ‘Ž‹‰‘•ƒ Šƒ”‹†‡•ǤŠ‡‹•ƒŽ•‘ƒ‹’‘”–ƒ–‹–”ƒ ‡ŽŽ—Žƒ”ƒʹΪ•–‘”‡ˆ‘”–Š‡ ‡ŽŽǤ ‹ƒŽŽ›ǡ‹– ‹• ƒ •‹–‡ ™Š‡”‡ „‹‘Ž‘‰‹ ƒŽ ‡„”ƒ‡• ƒ”‡ ƒ••‡„Ž‡†ǡ ƒ† ‹– ‹• ‹˜‘Ž˜‡† ‹ ˆƒ––› ƒ ‹† ƒ† ’Š‘•’Š‘Ž‹’‹† „‹‘•›–Š‡•‹• ͸ͺǡͻ͵ǡͳͷͺǤ – Š‘‡‘•–ƒ•‹•ǡ –Š‡ –Š”‡‡ ˆ— –‹‘• ‘ˆ –Š‡  ȋ’”‘–‡‹ ˆ‘Ž†‹‰ǡƒʹΪ•–‘”‡ƒ†‹–•ˆ— –‹‘ƒ•ƒ•‹–‡ˆ‘”ˆƒ––›ƒ ‹†ƒ†’Š‘•’Š‘Ž‹’‹†•›–Š‡•‹•Ȍƒ”‡‹. 20GeneralIntroduction.

(90) Chapter1 ƒ †›ƒ‹  ‡“—‹Ž‹„”‹—Ǥ ‹•–—”„ƒ ‡ ‘ˆ ƒ› ‘ˆ –Š‡ –Š”‡‡ Š‘‡‘•–ƒ–‹  ˆ— –‹‘• ‘ˆ –Š‡  Ž‡ƒ†•–‘•–”‡••ǡƒ†‹•ƒ‹ˆ‡•–‡†„›–Š‡ƒ ——Žƒ–‹‘‘ˆ—ˆ‘Ž†‡†’”‘–‡‹•Ǥ  •–”‡•• ƒ ƒ”‹•‡ –”ƒ•‹‡–Ž› ƒ• ƒ ‡ŽŽǯ• ‰‡‡ ‡š’”‡••‹‘ ’”‘‰”ƒ ‹• ƒŽ–‡”‡† ‹ ”‡•’‘•‡ –‘ Šƒ‰‹‰ ‡š–”ƒ ‡ŽŽ—Žƒ” •‹‰ƒŽ•Ǥ ‘” ‡šƒ’Ž‡ǡ Šƒ‰‹‰ ‡˜‹”‘‡–ƒŽ ‘†‹–‹‘• ƒ”‡•—Ž–‹ƒ‹ ”‡ƒ•‡†”‡“—‹”‡‡–ˆ‘”‡š–”ƒ ‡ŽŽ—Žƒ”‡œ›‡•ǡ™Š‹ Š‹–—” ƒ‘˜‡”™Š‡Ž–Š‡™‹–Š‡™Ž›•›–Š‡•‹•‡†’”‘–‡‹•™ƒ‹–‹‰–‘„‡ˆ‘Ž†‡†Ǥ‹‡™‹•‡ǡ–Š‹• ‘†‹–‹‘ ƒ ƒ”‹•‡ ‹ ‹†—•–”‹ƒŽ •–ƒ‹• ‘˜‡”’”‘†— ‹‰ Š‘‘Ž‘‰‘—• ‡œ›‡• —†‡” ‘’–‹‹•‡† ‘†‹–‹‘•Ǥ•–”‡•• ƒƒŽ•‘„‡ ƒ—•‡†„›‘–Š‡”‡˜‹”‘‡–ƒŽ’‡”–—”„ƒ–‹‘• –Š‡ ‡ŽŽ ‡ ‘—–‡”•Ǥ Š‡•‡ ‹ Ž—†‡ —–”‹‡– •–ƒ”˜ƒ–‹‘ǡ ƒ‘š‹ƒǡ ˜‹”ƒŽ ‹ˆ‡ –‹‘•ǡ ƒ† Š‡ƒ– ͳ͵ǡ͸ͲǡͺͷǤ.  •–”‡•• ƒ ƒŽ•‘ „‡ ‘”‡ ’‡”ƒ‡– ‹ ‡ŽŽ• –Šƒ– „‡ƒ” —–ƒ–‹‘• –Šƒ– ‹–‡”ˆ‡”‡ ™‹–Š ’”‘–‡‹ ƒ–—”ƒ–‹‘ ‹ –Š‡ ǡ ‘” ‹ ‡ŽŽ• –Šƒ– ‡š’”‡•• †‹ˆˆ‹ —Ž– –‘ ˆ‘Ž† Š‡–‡”‘Ž‘‰‘—• ’”‘–‡‹•Ǥ —”–Š‡”‘”‡ǡ •‡˜‡”ƒŽ Š‡‹ ƒŽ ƒ‰‡–• ƒ †‹•–—”„ –Š‡  ƒ† Ž‡ƒ† –‘ •–”‡••Ǥ ‡†— ‹‰ ƒ‰‡–• •— Š ƒ• EǦ‡” ƒ’–‘‡–Šƒ‘Ž ‘” ͳǡͶǦ†‹–Š‹‘–Š”‡‹–‘Ž ȋȌ †‹•–—”„ –Š‡ ‘š‹†ƒ–‹˜‡ ‡˜‹”‘‡– ‘ˆ –Š‡  ƒ† ”‡†— ‡ †‹•—Žˆ‹†‡ „‘†• –Š‡”‡„› ‹–‡”ˆ‡”‹‰ ™‹–Š –Š‡ ‘š‹†ƒ–‹˜‡ ’”‘–‡‹ ˆ‘Ž†‹‰ ‹ –Š‡ Ǥ Š‡ †”—‰ –—‹ ƒ› ‹ǡ ™Š‹ Š ‹• ’”‘†— ‡† „› –Š‡ „ƒ –‡”‹—Streptomyceslysosuperificus ͳͷ͹ǡ„Ž‘ •–Š‡’”‘†— –‹‘‘ˆǦŽ‹‡†‰Ž› ‘’”‘–‡‹• „› ‹””‡˜‡”•‹„Ž› ‹Š‹„‹–‹‰ –Š‡ ‡œ›‡ Ž   ’Š‘•’Š‘–”ƒ•ˆ‡”‡ƒ•‡ ȋ Ȍǡ ”‡•—Ž–‹‰ ‹ ƒ ——Žƒ–‹‘ ‘ˆ —ˆ‘Ž†‡† ’”‘–‡‹• ‹ –Š‡ Ǥ Š‡ ƒŽ ‹— ‹‘‘’Š‘”‡ ʹ͵ͳͺ͹ ‹†— ‡•  •–”‡•• „› †‡’Ž‡–‹‰ –Š‡  Ž—‹ƒŽ ƒʹΪ •–‘”‡Ǥ Š‹• ‹ –—” ‹Š‹„‹–• ’”‘–‡‹ ˆ‘Ž†‹‰ ƒ† ‹–‡”ˆ‡”‡• ™‹–Š —Ž–‹’Ž‡ ’”‘ ‡••‡• ‹ –Š‡  ‹ Ž—†‹‰ Šƒ’‡”‘‡ ˆ— –‹‘ ͳͳ͹ǡͳͷ͸ǡ .  ƒ –‹˜‹–›͵ǡƒ†–ƒ”‰‡–‹‰†—‡–‘†‡ ”‡ƒ•‡†DȋͳǦʹȌǦƒ‘•‹†ƒ•‡ƒ –‹˜‹–›͵ͶǤ ‘ ‘’‡ ™‹–Š ƒ† ƒ†ƒ’– –‘  •–”‡••ǡ ƒ ‹–”ƒ ‡ŽŽ—Žƒ” Ǧ–‘Ǧ— Ž‡—• •‹‰ƒŽ –”ƒ•†— –‹‘’ƒ–Š™ƒ›Šƒ•‡˜‘Ž˜‡†‹–Š‡‡—ƒ”›‘–‹  ‡ŽŽǤŠ‹••‹‰ƒŽ–”ƒ•†— –‹‘’ƒ–Š™ƒ› ‹•–‡”‡†–Š‡ˆ‘Ž†‡†”‘–‡‹‡•’‘•‡ȋȌǡƒ†ƒ –‹˜ƒ–‹‘‘ˆ–Š‹•’ƒ–Š™ƒ›–”‹‰‰‡”•ƒ ‡š–‡•‹˜‡–”ƒ• ”‹’–‹‘ƒŽ”‡•’‘•‡™Š‹ Šƒ†Œ—•–•–Š‡ˆ‘Ž†‹‰ ƒ’ƒ ‹–›‘ˆ–Š‡ǤŠ‡‹‹–‹ƒŽ –ƒ•‘ˆ–Š‡‹•–‘•ƒŽ˜ƒ‰‡—ˆ‘Ž†‡†’”‘–‡‹•„›‹ ”‡ƒ•‹‰–Š‡ˆ‘Ž†‹‰ ƒ’ƒ ‹–›‘ˆ–Š‡Ǥ ‘™‡˜‡”ǡ–Š‡ƒŽ•‘‡Šƒ ‡•–Š‡–ƒ”‰‡–‹‰‘ˆ—ˆ‘Ž†‡†’”‘–‡‹•‹–Š‡ˆ‘””‡ › Ž‹‰Ǥ Š‡ ’”‘–‡‹• ˆƒ‹Ž –‘ ‘„–ƒ‹ –Š‡‹” ’”‘’‡” ˆ‘Ž†ǡ ‡˜‡ ƒˆ–‡” •‡˜‡”ƒŽ ˆ‘Ž†‹‰ ƒ––‡’–•ǡ –Š‡› Šƒ˜‡ –‘ „‡ ”‡‘˜‡† ˆ”‘ –Š‡ Ǥ Š‡•‡ ‹•ˆ‘Ž†‡† ’”‘–‡‹• ‘—Ž† ‘–Š‡”™‹•‡ ƒ ——Žƒ–‡ǡ ƒ‰‰”‡‰ƒ–‡ƒ†„‡ ‘‡–‘š‹ ˆ‘”–Š‡ ‡ŽŽǤ‡ˆˆ‹ ‹‡–’”‘–‡‘Ž›–‹ •›•–‡‹•–Š‡”‡ˆ‘”‡ ‘—’Ž‡† –‘ –Š‡ “—ƒŽ‹–› ‘–”‘Ž ƒ Š‹‡”› ‘ˆ –Š‡  –‘ †‹•’‘•‡ ‘ˆ –Š‡•‡ –‡”‹ƒŽŽ› ‹•ˆ‘Ž†‡† ’”‘–‡‹•Ǥ ™‘”‘—–‡•ƒ”‡‘™–Šƒ––ƒ”‰‡––Š‡•‡‹•ˆ‘Ž†‡†’”‘–‡‹•ˆ‘”†‡‰”ƒ†ƒ–‹‘ǣȋ‹ȌǦ ƒ••‘ ‹ƒ–‡† †‡‰”ƒ†ƒ–‹‘ ȋȌ ‹ ™Š‹ Š –Š‡ ‹•ˆ‘Ž†‡† ’”‘–‡‹• ƒ”‡ ”‡–”‘–”ƒ•Ž‘ ƒ–‡† –‘ –Š‡ ›–‘•‘Žǡ—„‹“—‹–‹ƒ–‡†ƒ††‡‰”ƒ†‡†„›–Š‡ʹ͸’”‘–‡ƒ•‘‡ͻͳǡͳ͵ͷǡƒ†ȋ‹‹Ȍ—–‘’Šƒ‰›‹ ™Š‹ Š’ƒ”–•‘ˆ–Š‡ƒ”‡–ƒ”‰‡–‡†–‘Ž›•‘•‘‡•‘”˜ƒ —‘Ž‡•͹ͷǤ. GeneralIntroduction21.

(91) Chapter1 TheUnfoldedProteinResponseinS.cerevisiae Š‡  ™ƒ• ˆ‹”•– Šƒ”ƒ –‡”‹•‡† ‹ S. cerevisiaeǡ ™Š‡”‡ ‰‡‡–‹  • ”‡‡• ‹†‡–‹ˆ‹‡† –Š”‡‡ ’”‘–‡‹• –Šƒ– ™‡”‡ ”‡“—‹”‡† ˆ‘” –Š‡ •‹‰ƒŽ –”ƒ•†— –‹‘ ˆ”‘ –Š‡  –‘ –Š‡ — Ž‡—•ǣ ƒ –”ƒ•‡„”ƒ‡•‡”‹‡Ȁ–Š”‡‘‹‡‹ƒ•‡ǡ

(92) ”‡ͳ’ʹͳǡƒ„ƒ•‹ Ž‡— ‹‡œ‹’’‡”–›’‡–”ƒ• ”‹’–‹‘ ˆƒ –‘” ƒ ͳ’ ʹʹǡͻͷǡƒ†ƒ–Ž‹‰ƒ•‡ǡŽ‰ͳ’ ͳͷͳǤŠ‡”‘Ž‡‘ˆ–Š‡•‡–Š”‡‡ ‘’‘‡–•‹–Š‡ ›‡ƒ•–‹•• Š‡ƒ–‹•‡†‹ ‹‰—”‡͸Ǥ

(93) ”‡ͳ’‹•ƒ –‹˜ƒ–‡†„›–Š‡ƒ ——Žƒ–‹‘‘ˆ—ˆ‘Ž†‡†’”‘–‡‹•‹–Š‡ǡƒ†ˆƒ ‹Ž‹–ƒ–‡• –‘‰‡–Š‡”™‹–ŠŽ‰ͳ’–Š‡•’Ž‹ ‹‰‘ˆƒ— ‘˜‡–‹‘ƒŽ‹–”‘ˆ”‘HAC1Ǥ‡‘˜ƒŽ‘ˆ –Š‡ — ‘˜‡–‹‘ƒŽ ‹–”‘ ˆ”‘ –Š‡ HAC1  ‡ƒ„Ž‡• –Š‡ ‡ˆˆ‹ ‹‡– –”ƒ•Žƒ–‹‘ ‘ˆ –Š‡ ‡••‡‰‡” ƒ† –Š‡ •—„•‡“—‡– •›–Š‡•‹• ‘ˆ ƒ –‹˜‡ ƒ ͳ’ ’”‘–‡‹Ǥ Š‡ ƒ –‹˜‡ ƒ ͳ’ –”ƒ•Ž‘ ƒ–‡• –‘ –Š‡ — Ž‡—•ǡ ™Š‡”‡ ‹– ’”‘‘–‡• –”ƒ• ”‹’–‹‘ ‘ˆ ‹–• –ƒ”‰‡– ‰‡‡• „› ƒ ‹–‡”ƒ –‹‘™‹–Š–Š‡—ˆ‘Ž†‡†’”‘–‡‹”‡•’‘•‡‡Ž‡‡–ȋ•Ȍǡ’”‡•‡–‹–Š‡’”‘‘–‡”• ‘ˆ Ǧ”‡‰—Žƒ–‡† ‰‡‡• •— Š ƒ• ‰‡‡• ‡ ‘†‹‰  Šƒ’‡”‘‡• ƒ† ˆ‘Ž†ƒ•‡•Ǥ Š‡  –ƒ”‰‡– ‰‡‡• ‘ˆ ›‡ƒ•– Šƒ˜‡ „‡‡ †‡ˆ‹‡† „› ‹ ”‘ƒ””ƒ› ‡š’”‡••‹‘ ’”‘ˆ‹Ž‹‰ ͳ͸ͲǤ Š‡› ‘’”‹•‡ ͵ͺͳ ‰‡‡• ™Š‹ Š ‹• ‘”‡ –Šƒ ͷΨ ‘ˆ –Š‡ ›‡ƒ•– ‰‡‘‡Ǥ ‘‰ –Š‡  –ƒ”‰‡– ‰‡‡• ƒ”‡ ƒ› ’”‘–‡‹• –Šƒ– ’Žƒ› ”‹–‹ ƒŽ ”‘Ž‡• ‹ –Š‡ ǡ –Š‡ ‘Ž‰‹ ƒ† –Š”‘—‰Š‘—– –Š‡ •‡ ”‡–‘”›’ƒ–Š™ƒ›Ǥ ‡ ‡ǡ–Š‡ ƒ„‡–Š‘—‰Š–‘ˆƒ•ƒŠ‘‡‘•–ƒ–‹  ‘–”‘Ž‡ Šƒ‹• –‘”‡‘†‡Ž–Š‡•‡ ”‡–‘”›’ƒ–Š™ƒ›ƒ ‘”†‹‰–‘–Š‡ ‡ŽŽǯ•‡‡†Ǥ   Ire1p

(94) ”‡ͳ’ ȋ‹‘•‹–‘Ž ”‡“—‹”‹‰ ͳȌ ™ƒ• ‘”‹‰‹ƒŽŽ› ‹†‡–‹ˆ‹‡† ‘ –Š‡ „ƒ•‹• ‘ˆ ‹–• ”‘Ž‡ ‹ ‹‘•‹–‘Ž ’”‘–‘–”‘’Š›‹S.cerevisiae ͳͲ͸Ǥ ‘™‡˜‡”ǡ•‘‘–Š‡”‡ƒˆ–‡”ǡ–™‘‘–Š‡”‰”‘—’•Ž‹‡†

(95) ”‡ͳ’–‘ –Š‡ǡ•‹ ‡‹–™ƒ•”‡“—‹”‡†ˆ‘”–Š‡ƒ –‹˜ƒ–‹‘‘ˆ–Š‡KAR2ȋ‹Ȍ‰‡‡—’‘Ǧ•–”‡••ʹͳǡͻ͸Ǥ Š‡ S. cerevisiae IRE1 ‰‡‡ ‡ ‘†‡• ƒ –›’‡

(96)  –”ƒ•‡„”ƒ‡ ’”‘–‡‹ ‘•‹•–‹‰ ‘ˆ ͳͳͳͷ ƒ‹‘ ƒ ‹†• –Šƒ– ”‡•‹†‡• ‹ –Š‡  ‡„”ƒ‡Ǥ ‡‘‡ ™‹†‡ ƒƒŽ›•‹• ‹†‡–‹ˆ‹‡† HAC1  ƒ• –Š‡ ‘Ž› •—„•–”ƒ–‡ ˆ‘”

(97) ”‡ͳ’ ͳͲ͹Ǥ

(98) ”‡ͳ’ ‹• –Š‡ ‘•– ’”‘š‹ƒŽ ‘’‘‡– ‘ˆ –Š‡ ’ƒ–Š™ƒ›ǡ ƒ† ‘•‹•–• ‘ˆ –Š”‡‡ ˆ— –‹‘ƒŽ †‘ƒ‹•Ǥ  Ž—‹ƒŽ †‘ƒ‹ǡ ƒ •‡”‹‡Ǧ–Š”‡‘‹‡ ‹ƒ•‡ †‘ƒ‹ ƒ† ƒ ƒ•‡ †‘ƒ‹Ǥ Š‡ Ž—‹ƒŽ †‘ƒ‹ ‹• –Š‡ ‘•– ƒ‹‘Ǧ–‡”‹ƒŽ †‘ƒ‹–Šƒ–”‡•‹†‡•‹–Š‡Ž—‡‘ˆ–Š‡ƒ†ˆ— –‹‘•ƒ•–Š‡•‡•‘”‘ˆ–Š‡ˆ‘Ž†‹‰•–ƒ–‡ ‘ˆ’”‘–‡‹•‹–Š‡ʹͳǤ

(99) ”‡ͳ’•‡•‡•–Š‡Ž‘ƒ†‘ˆ‹•ˆ‘Ž†‡†’”‘–‡‹•ȋƒ–Ž‡ƒ•–’ƒ”–Ž›Ȍ–Š”‘—‰Š „‹†‹‰™‹–Š— ‘’Ž‡š‡†‹͹ͲǡͳͳͷǤ ——Žƒ–‹‘‘ˆ—ˆ‘Ž†‡†’”‘–‡‹•‹–Š‡”‡•—Ž–•‹ –Š‡ ”‡Ž‡ƒ•‡ ‘ˆ ‹ ˆ”‘

(100) ”‡ͳ’ ƒ† ƒ—•‡•

(101) ”‡ͳ’ –‘ ‘Ž‹‰‘‡”‹•‡ ƒ† –‘ —†‡”‰‘ –”ƒ•Ǧ ƒ—–‘’Š‘•’Š‘”›Žƒ–‹‘˜‹ƒ‹–• ›–‘•‘Ž‹ •‡”‹‡Ǧ–Š”‡‘‹‡‹ƒ•‡†‘ƒ‹ ͳͶ͹ǡͳ͹ͺǤŠ‹•ƒ –‹˜ƒ–‡• ‹–—”–Š‡•‹–‡Ǧ•’‡ ‹ˆ‹ ‡†‘”‹„‘— Ž‡ƒ•‡ȋƒ•‡Ȍ†‘ƒ‹Ž‘ ƒ–‡†ƒ––Š‡ ƒ”„‘š›Ǧ–‡”‹—• ‘ˆ

(102) ”‡ͳ’Ǥˆ–‡”„‡‹‰ƒ –‹˜ƒ–‡†ǡ–Š‡‡†‘”‹„‘— Ž‡ƒ•‡†‘ƒ‹‘ˆ

(103) ”‡ͳ’ǡ‹ ‘Œ— –‹‘™‹–Š Ž‰ͳ’ǡ’”‘ ‡••‡•–Š‡HAC1„›•’Ž‹ ‹‰ƒ— ‘˜‡–‹‘ƒŽ‹–”‘ˆ”‘–Š‡‡••‡‰‡” ͳͷʹǤ. 22GeneralIntroduction.

(104) Chapter1                     . Figure6. Š‡ƒ–‹ ‘˜‡”˜‹‡™‘ˆ–Š‡‹›‡ƒ•–ǤͳǤ

(105) ƒ‘Ǧ•–”‡•••‹–—ƒ–‹‘–Š‡’”‘š‹ƒŽ•‡•‘” ‹ƒ•‡

(106) ”‡ͳ’‹•Š‡Ž†‹ƒ‘‘‡”‹ ‹ƒ –‹˜‡•–ƒ–‡„›–Š‡ Šƒ’‡”‘‡‹ǤʹǤ’‘ƒ ——Žƒ–‹‘‘ˆ —ˆ‘Ž†‡† ’”‘–‡‹• ‹ –Š‡  

(107)  †‹••‘ ‹ƒ–‡• ˆ”‘

(108) ”‡ͳ’ ƒ† ƒ••‘ ‹ƒ–‡• ™‹–Š –Š‡ —ˆ‘Ž†‡† ’”‘–‡‹•Ǥ Š‡ ”‡Ž‡ƒ•‡†

(109) ”‡ͳ’ —†‡”‰‘‡• †‹‡”‹œƒ–‹‘ ƒ† ƒ—–‘’Š‘•’Š‘”›Žƒ–‹‘ ƒ† ƒ •‹–‡Ǧ •’‡ ‹ˆ‹  ‡†‘— Ž‡ƒ•‡ ȋƒ•‡Ȍ †‘ƒ‹ ‹• ƒ –‹˜ƒ–‡†Ǥ ͵Ǥ Š‡ ƒ•‡ Ž‡ƒ˜‡• ƒ — ‘˜‡–‹‘ƒŽ ‹–”‘ˆ”‘–Š‡HAC1ǤͶǤŠ‡HAC1‡š‘‡†•ƒ”‡Œ‘‹‡†–‘‰‡–Š‡”„›–Ž‹‰ƒ•‡ǤͷǤ Š‡‹†— ‡†HAC1‹•‡ˆˆ‹ ‹‡–Ž›–”ƒ•Žƒ–‡†–‘ ƒ ͳ’Ǥ͸Ǥ ƒ ͳ’–”ƒ•Ž‘ ƒ–‡•–‘–Š‡— Ž‡—• ƒ† „‹†• –‘ Ǧ‡Ž‡‡–• ’”‡•‡– ‹ –Š‡ ’”‘‘–‡”• ‘ˆ ‹–• –ƒ”‰‡– ‰‡‡•Ǥ ͹Ǥ ”ƒ• ”‹’–‹‘ ‘ˆ ‰‡‡•‡ ‘†‹‰ˆ‘Ž†ƒ•‡•ƒ† Šƒ’‡”‘‡•‹•‹†— ‡†ǡŽ‡ƒ†‹‰–‘ƒ‹ ”‡ƒ•‡†ˆ‘Ž†‹‰ ƒ’ƒ ‹–›‘ˆ –Š‡ Ǥ ͺǤ Š‡ –Š‡ ‘†‹–‹‘• ‹ –Š‡  ƒ”‡ ‘”ƒŽ‹œ‡† –Š‡  ‹• •™‹– Š‡† ‘ˆˆ „› †‡’Š‘•’Š‘”›Žƒ–‹‘ƒ††‡’‘Ž›‡”‹•ƒ–‹‘‘ˆ

(110) ”‡ͳ’ ‘†— –‡†„›–Š‡‹ƒ•‡– ʹ’Ǥ. GeneralIntroduction23.

(111) Chapter1  ‘™‡˜‡”ǡ†‹••‘ ‹ƒ–‹‘‘ˆ‹ˆ”‘

(112) ”‡ͳ’‹•‘–•—ˆˆ‹ ‹‡–ˆ‘”ƒ –‹˜ƒ–‹‘‘ˆ–Š‡Ǥ‡Ž‡–‹‘ ‘ˆ–Š‡‹„‹†‹‰•‹–‡”‡†‡”‡†

(113) ”‡ͳ’—ƒŽ–‡”‡†‹•–”‡••‹†— ‹„‹Ž‹–›Ǥ

(114) –™ƒ•‹ƒ –‹˜‡‹ —•–”‡••‡† ‡ŽŽ•„—–•–‹ŽŽƒ„Ž‡–‘ƒ –‹˜ƒ–‡–Š‡’ƒ–Š™ƒ›—’‘•–”‡•• ͹ͳǡͳͳ͵Ǥ–”— –—”ƒŽ ƒƒŽ›•‡•‹†‹ ƒ–‡†–Šƒ–

(115) ”‡ͳ’‹‰Š–‹–‡”ƒ –†‹”‡ –Ž›™‹–Š—ˆ‘Ž†‡†’”‘–‡‹•ǤƒŽ›•‹•‘ˆ–Š‡ ”›•–ƒŽ •–”— –—”‡ ‘ˆ –Š‡ ‘”‡  Ž—‹ƒŽ †‘ƒ‹ ȋ Ȍ ”‡˜‡ƒŽ‡† –Š‡ ’”‡•‡ ‡ ‘ˆ ƒ †‡‡’ ‰”‘‘˜‡ ‹  †‹‡”•ǡ ƒ ‰”‘‘˜‡ –Šƒ– ”‡•‡„Ž‡• –Š‡ ƒŒ‘” Š‹•–‘ ‘’ƒ–‹„‹Ž‹–› ‘’Ž‡š ȋ ȌǦŽ‹‡’‡’–‹†‡„‹†‹‰‰”‘‘˜‡ʹ͵ǤŠ‡†‡’–Š‘ˆ–Š‡‰”‘‘˜‡™‘—Ž†ƒŽŽ‘™ˆ‘”‹–‡”ƒ –‹‘• ™‹–Š —ˆ‘Ž†‡† ”‡‰‹‘• ‘ˆ ’”‘–‡‹• „—– ’”‡ Ž—†‡• ‹–‡”ƒ –‹‘ ™‹–Š ‘’ƒ –Ž› ˆ‘Ž†‡† ’”‘–‡‹•Ǥ —”–Š‡”‘”‡ǡ —–ƒ–‹‘• ‹ ”‡•‹†—‡• Ž‹‹‰ –Š‡ „‘––‘ ‘ˆ –Š‡ ‰”‘‘˜‡ǡ ‘” ƒ– –Š‡ ‹–‡”ˆƒ ‡ ‘ˆ –Š‡ †‹‡”• ƒ„‘Ž‹•Š‡†

(116) ”‡ͳ’ ƒ –‹˜ƒ–‹‘Ǥ Š‡•‡ ˆ‹†‹‰• Šƒ˜‡ Ž‡† –‘ –Š‡ Š›’‘–Š‡•‹• –Šƒ–

(117) ”‡ͳ’ †‹”‡ –Ž› „‹†• —ˆ‘Ž†‡† ’”‘–‡‹• ˜‹ƒ ‹–• Ǥ ‹†‹‰ ‘ˆ

(118) ”‡ͳ’ –‘ —ˆ‘Ž†‡†”‡‰‹‘•ƒ›’”‘‘–‡–Š‡†‹‡”‹•ƒ–‹‘™Š‹ Š‹•‡ ‡••ƒ”›–‘ˆ‘”–Š‡‰”‘‘˜‡ǤŠ‡ Šƒ‰‡• ‹ –Š‡ Ž—‹ƒŽ †‘ƒ‹ ‘ˆ

(119) ”‡ͳ’ ‹ –—” ’‘•‹–‹‘

(120) ”‡ͳ’ ‹ƒ•‡ †‘ƒ‹• ‹ –Š‡ ›–‘’Žƒ• ‘’–‹ƒŽŽ› ˆ‘” ƒ—–‘’Š‘•’Š‘”›Žƒ–‹‘ –‘ ‹‹–‹ƒ–‡ –Š‡ Ǥ

(121)  –Š‹• ‘†‡Ž —ˆ‘Ž†‡† ’”‘–‡‹•ƒ –ƒ•’‘•‹–‹˜‡”‡‰—Žƒ–‘”•‘ˆ

(122) ”‡ͳ’ǡ™Š‡”‡ƒ•‹™‘—Ž†ƒ –ƒ•ƒ‡‰ƒ–‹˜‡”‡‰—Žƒ–‘” ƒ†™‘—Ž†„‡‘”‡ƒƒ†Œ—•–‡”ˆ‘”•‡•‹–‹˜‹–›–‘•–”‡••͹ͳǤ Š‡ ‡šƒ – Ž‘ ƒŽ‹•ƒ–‹‘ ‘ˆ –Š‡ Ǧ–‡”‹ƒŽ †‘ƒ‹ ‘ˆ

(123) ”‡ͳ’ Šƒ• „‡‡ •‘‡™Šƒ– — Ž‡ƒ”Ǥ

(124) ‘”†‡”–‘•‡•‡–Š‡ˆ‘Ž†‹‰•–ƒ–‡‘ˆ–Š‡ƒ†–”ƒ•‹––Š‡•‹‰ƒŽ–‘–Š‡ HAC1 ǡ –Š‡ Ǧ–‡”‹ƒŽ †‘ƒ‹ ‘ˆ

(125) ”‡ͳ’ —•– „‡ Ž‘ ƒŽ‹•‡† ‹ –Š‡ ˜‹ ‹‹–› ‘ˆ ‹–• •—„•–”ƒ–‡ ȋHAC1 Ȍǡ ƒ† – Ž‹‰ƒ•‡Ǥ Ž•‘ǡ †ƒͷ’ǡ ™Š‹ Š ‹• ’ƒ”– ‘ˆ –Š‡ ͷ –”ƒ• ”‹’–‹‘ƒŽ ‘ƒ –‹˜ƒ–‘” ‘’Ž‡š‘ˆ›‡ƒ•–ǡ™Š‹ Š™ƒ••Š‘™–‘‹–‡”ƒ –™‹–Š

(126) ”‡ͳ’ƒ†„‡”‡“—‹”‡†ˆ‘” HAC1•’Ž‹ ‹‰ͳͺͲ•Š‘—Ž†„‡ƒ ‡••‹„Ž‡ˆ‘”

(127) ”‡ͳ’Ǥ Š‡ — Ž‡ƒ” Ž‘ ƒŽ‹•ƒ–‹‘ ‘ˆ †ƒͷ’ ƒ† –Šƒ– ‘ˆ – Ž‹‰ƒ•‡ ͳ͸ –‘‰‡–Š‡” ™‹–Š –Š‡ ƒ••—’–‹‘ –Šƒ– ‘Ž› ‡™Ž› •›–Š‡•‹•‡† HAC1  ™‘—Ž† „‡ •—„•–”ƒ–‡ ˆ‘”

(128) ”‡ͳ’ ‡†‹ƒ–‡†•’Ž‹ ‹‰ǡŽ‡†–‘–Š‡Š›’‘–Š‡•‹•–Šƒ––Š‡

(129) ”‡ͳ’ ƒ– Š‡•HAC1†—”‹‰‡š’‘”– ˆ”‘ –Š‡ — Ž‡—• –‘ –Š‡ ›–‘•‘Ž ͳͷͳǤ

(130) ”‡ͳ’ ™‘—Ž† –Š—• „‡ Ž‘ ƒŽ‹•‡† –‘ –Š‡  ƒ† ‹‡” — Ž‡ƒ” ‡„”ƒ‡ ™Š‹ Š ƒ”‡ ‘–‹‰—‘—• ™‹–Š ‡ƒ Š ‘–Š‡”Ǥ

(131) –• Ǧ–‡”‹ƒŽ ŠƒŽˆ ™‹–Š –Š‡ ‡†‘”‹„‘— Ž‡ƒ•‡†‘ƒ‹™‘—Ž†–Š—•ˆƒ ‡–Š‡ ›–‘’Žƒ•‘”–Š‡— Ž‡—•ǤŠ‡”‡ ‡–ˆ‹†‹‰ ‘ˆ ƒ — Ž‡ƒ” Ž‘ ƒŽ‹•ƒ–‹‘ •‡“—‡ ‡ ‹ –Š‡ Ž‹‡” ”‡‰‹‘ ‘ˆ

(132) ”‡ͳ’ ƒŽ•‘ ‹†‹ ƒ–‡† –Š‡ — Ž‡ƒ” Ž‘ ƒŽ‹•ƒ–‹‘‘ˆ–Š‡Ǧ–‡”‹ƒŽ†‘ƒ‹ ͶʹǤ ‘™‡˜‡”ǡ‡ƒ”Ž‹‡”‹–™ƒ•ƒŽ•‘”‡’‘”–‡†–Šƒ–•’Ž‹ ‹‰ ‘ˆHAC1’”‡ —”•‘”•–Šƒ–Šƒ˜‡ƒ ——Žƒ–‡†‘•–ƒŽŽ‡†’‘Ž›”‹„‘•‘‡• ‘—Ž†‘ —”‹ –Š‡ ›–‘’Žƒ•ͳ͵͹Ǥ

(133) –™ƒ•–Š‡”‡ˆ‘”‡•—‰‰‡•–‡†–Šƒ––Š‡‹’‘”–‘ˆ

(134) ”‡ͳ’‹–‘–Š‡— Ž‡—•‹•‘– ”‡“—‹”‡† ˆ‘” –Š‡ ’”‘ ‡••‹‰ ‘ˆ –Š‡ ’”‡‡š‹•–‹‰ ’‘‘Ž ‘ˆ •–ƒŽŽ‡† ’‘Ž›”‹„‘•‘‡Ǧƒ••‘ ‹ƒ–‡† HAC1‹‡†‹ƒ–‡Ž›—’‘‹†— –‹‘‘ˆ•–”‡••ǤŽ›‹ˆ–Š‡ ‘–‹—‡•ǡ— Ž‡ƒ” ‹’‘”–‘ˆ

(135) ”‡ͳ’‹•‡••‡–‹ƒŽˆ‘”–Š‡•’Ž‹ ‹‰‘ˆ‡™Ž›•›–Š‡•‹•‡†HAC1’”‡ —”•‘”‹ –Š‡— Ž‡—•ͶʹǤ. 24GeneralIntroduction.

(136) Chapter1 Hac1p HAC1  ‡ ‘†‡• –Š‡ „ƒ•‹  Ž‡— ‹‡ œ‹’’‡” ȋ„

(137) Ȍ –”ƒ• ”‹’–‹‘ ˆƒ –‘” –Šƒ– —Ž–‹ƒ–‡Ž› —’”‡‰—Žƒ–‡•–Š‡–”ƒ• ”‹’–‹‘‘ˆ–ƒ”‰‡–•‰‡‡•ǤHAC1ȋƒƒ ”‘›ˆ‘”ǣŠ‘‘Ž‘‰‘—•–‘ ATFȀCREB1Ȍ ™ƒ• ‘”‹‰‹ƒŽŽ› Ž‘‡† ƒ• ƒ —Ž–‹ ‘’› •—’’”‡••‘” ‘ˆ –Š‡ Schizosaccharomyces pombe † ͳͲǦͳʹͻ—–ƒ– ͳͳͲǤƒ–‡”‹–™ƒ• Ž‘‡†ƒ‰ƒ‹—•‹‰ƒ›‡ƒ•–‘‡ǦŠ›„”‹†• ”‡‡‹‰ǡ ƒ†‹–•”‘Ž‡‹–Š‡™ƒ•†‹• ‘˜‡”‡† ͻͷǤ†‡”‘Ǧ•–”‡••‡† ‘†‹–‹‘•ǡ–Š‡HAC1‰‡‡‹• ‘•–‹–—–‹˜‡Ž›–”ƒ• ”‹„‡†ǡ„—––Š‡HAC1uȋǮ—ˆ‘”—‹†— ‡†ǯȌ‹•’‘‘”Ž›–”ƒ•Žƒ–‡††—‡ –‘ ƒ — ‘˜‡–‹‘ƒŽ ‹–”‘ ‡ƒ” –Š‡ ͵ǯǦ‡† ‘ˆ –Š‡ –”ƒ• ”‹’– ͸͸ǡͳ͵͹ ȋ ‹‰Ǥ ͹ȌǤ ‹”•– ƒˆ–‡” •’Ž‹ ‹‰‘ˆ–Š‡‹Š‹„‹–‘”›‹–”‘„›–Š‡ƒ –‹‘‘ˆ

(138) ”‡ͳ’ƒ†Ž‰ͳ’‹•–Š‡‡™HAC1iȋǮ‹ǯ ˆ‘” ‹†— ‡†Ȍ ‡ˆˆ‹ ‹‡–Ž› –”ƒ•Žƒ–‡† –‘ ’”‘†— ‡ –Š‡ ƒ –‹˜‡ –”ƒ• ”‹’–‹‘ ˆƒ –‘” ƒ ͳ’ ͳͶǡ͸͸Ǥ ƒ ͳ’–Š‡–”ƒ•Ž‘ ƒ–‡•–‘–Š‡— Ž‡—•™Š‡”‡‹–ƒ –‹˜ƒ–‡•‘”‹ ”‡ƒ•‡•–”ƒ• ”‹’–‹‘‘ˆ –ƒ”‰‡– ‰‡‡• „› „‹†‹‰ –‘  •’‡ ‹ˆ‹  —’•–”‡ƒ ƒ –‹˜ƒ–‹‘ •‡“—‡ ‡•ǡ –Š‡ —ˆ‘Ž†‡† ’”‘–‡‹”‡•’‘•‡‡Ž‡‡–ȋȌ ʹʹǤŠ‡•’Ž‹ ‹‰‘ˆHAC1‹•–Š‡”‡ˆ‘”‡”‡‰ƒ”†‡†ƒ• –Š‡‡›”‡‰—Žƒ–‘”›•–‡’‹–Š‡’ƒ–Š™ƒ›‘ˆS.cerevisiaeǤ. Figure7. ‘˜‡–‹‘ƒŽ‹–”‘•’Ž‹ ‹‰‘ˆ–Š‡›‡ƒ•–HAC1 Ǥ (A) Š‡ͳǤͶ„HAC1u  ‘–ƒ‹•ƒ ‡ ‘†‹‰ƒʹ͵Ͳƒ‹‘ƒ ‹†’”‘–‡‹Ǥ’Ž‹ ‹‰‘ˆƒʹͷʹ–— ‘˜‡–‹‘ƒŽ‹–”‘ ˆ”‘ –Š‡ HAC1u ǡ Šƒ‰‡• –Š‡ Ǧ–‡”‹ƒŽ –ƒ‹Ž ‘ˆ –Š‡ ‡ ‘†‡† ’”‘–‡‹Ǥ Š‡ Žƒ•– ͳͲ ƒ‹‘ ƒ ‹†•‘ˆ–Š‡‡ ‘†‡†’”‘–‡‹ƒ”‡”‡’Žƒ ‡†™‹–Šƒƒ –‹˜ƒ–‹‘†‘ƒ‹‘ˆͳͺƒ‹‘ƒ ‹†•ǤŠ‡†ƒ” ‰”‡›„‘š”‡’”‡•‡–•–Š‡’ƒ”–‡ ‘†‹‰–Š‡Ǧ–‡”‹ƒŽͳͲƒ‹‘ƒ ‹†•‹HAC1uǤŠ‡„Žƒ  „‘š ”‡’”‡•‡–• –Š‡ ’ƒ”– ‡ ‘†‹‰ –Š‡ ͳͺ ƒ‹‘ ƒ ‹† ƒ –‹˜ƒ–‹‘ †‘ƒ‹Ǥ (B) Š‡ •–‡ǦŽ‘‘’ •–”— –—”‡‘ˆ–Š‡‹–”‘„‘”†‡”•‘ˆHAC1ǤŠ‡

(139) ”‡ͳ’ Ž‡ƒ˜ƒ‰‡•‹–‡•ƒ”‡‹†‹ ƒ–‡†„›ƒ””‘™• Ͷ͵Ǥ. GeneralIntroduction25.

(140) Chapter1 SpliceosomeIndependentSplicingofHAC1umRNA Š‡ •’Ž‹ ‡‘•‘‡Ǧ‹†‡’‡†‡– •’Ž‹ ‹‰ ‘ˆ –Š‡ HAC1u ǡ ‡†‹ƒ–‡† „›

(141) ”‡ͳ’ ƒ† Ž‰ͳ’ ”‡•‡„Ž‡•–Š‡’”‘ ‡••‘ˆ–•’Ž‹ ‹‰Ǥ ‡‘‡Ǧ™‹†‡ƒƒŽ›•‹•‹†‡–‹ˆ‹‡†HAC1uƒ• –Š‡ ‘Ž› •—„•–”ƒ–‡ ˆ‘”

(142) ”‡ͳ’ǡ •—‰‰‡•–‹‰ –Šƒ– –Š‹• — ‘˜‡–‹‘ƒŽ  ’”‘ ‡••‹‰ Šƒ• ‡˜‘Ž˜‡†•‘Ž‡Ž›ˆ‘”–Š‡•‹‰ƒŽ–”ƒ•†— –‹‘„‡–™‡‡ƒ†— Ž‡—• ͳͲ͹ǤŠ‡— ‘˜‡–‹‘ƒŽ ‹–”‘ ‘ˆ HAC1u  ‹• ʹͷʹ – Ž‘‰ ʹʹǡ ƒ† –Š‡ ‹–”‘ „‘”†‡”• ƒ† •’Ž‹ ‡Ǧ•‹–‡• ƒ”‡ ‘”‰ƒ‹•‡† ‹ –™‘ •–ƒ„Ž‡ •–‡ǦŽ‘‘’ •–”— –—”‡• ȋ ‹‰Ǥ ͹ȌǤ Š‡•‡ •ƒŽŽ •–‡ǦŽ‘‘’ •–”— –—”‡• ƒ”‡–Š‡•—„•–”ƒ–‡•ˆ‘”

(143) ”‡ͳ’ƒ†–Š‡ Ž‡ƒ˜ƒ‰‡ƒ––Š‡–™‘•’Ž‹ ‡Ǧ•‹–‡•‘ˆHAC1u‘ —”• ‹†‡’‡†‡–Ž› ƒ† ‹ ƒ ”ƒ†‘ ‘”†‡”Ǥ

(144) – ”‡“—‹”‡• ƒ ™‡ŽŽ †‡ˆ‹‡† ͹Ǧ— Ž‡‘–‹†‡ Ž‘‘’ –Šƒ– —•– „‡ Ž‘•‡† „› ƒ •–‡Ǥ ˆ–‡” ‡š ‹•‹‘ ‘ˆ –Š‡ ‹–”‘ „›

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Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger Mulder, H.J... Unraveling the stepwise activation

Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger

Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger Mulder, H.J... Unraveling the stepwise activation

Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger

Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger Mulder, H.J... Unraveling the stepwise activation

Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger

Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger..

Protein secretion in the filamentous fungus Aspergillus niger Weenink, X.O

Het feit dat het Gla-GFP fusie-eiwit in een srgC disruptie stam deels in kleine organellen terecht komt, suggereert dat het SrgC eiwit niet alleen bij de transportstap van