Sumoylation regulates EXO1 stability and processing of DNA damage

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F15%3A00081061" target="_blank" >RIV/00216224:14110/15:00081061 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00159816:_____/15:00063107

Výsledek na webu

<a href="http://dx.doi.org/10.1080/15384101.2015.1060381" target="_blank" >http://dx.doi.org/10.1080/15384101.2015.1060381</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/15384101.2015.1060381" target="_blank" >10.1080/15384101.2015.1060381</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Sumoylation regulates EXO1 stability and processing of DNA damage

Popis výsledku v původním jazyce

DNA double-strand break repair by the error-free pathway of homologous recombination (HR) requires the concerted action of several factors. Among these, EXO1 and DNA2/BLM are responsible for the extensive resection of DNA ends to produce 3'-overhangs, which are essential intermediates for downstream steps of HR. Here we show that EXO1 is a SUMO target and that sumoylation affects EXO1 ubiquitylation and protein stability. We identify an UBC9-PIAS1/PIAS4-dependent mechanism controlling human EXO1 sumoylation in vivo and demonstrate conservation of this mechanism in yeast by the Ubc9-Siz1/Siz2 using an in vitro reconstituted system. Furthermore, we show physical interaction between EXO1 and the de-sumoylating enzyme SENP6 both in vitro and in vivo, promoting EXO1 stability. Finally, we identify the major sites of sumoylation in EXO1 and show that ectopic expression of a sumoylation-deficient form of EXO1 rescues the DNA damage-induced chromosomal aberrations observed upon wt-EXO1 express

Název v anglickém jazyce

Sumoylation regulates EXO1 stability and processing of DNA damage

Popis výsledku anglicky

DNA double-strand break repair by the error-free pathway of homologous recombination (HR) requires the concerted action of several factors. Among these, EXO1 and DNA2/BLM are responsible for the extensive resection of DNA ends to produce 3'-overhangs, which are essential intermediates for downstream steps of HR. Here we show that EXO1 is a SUMO target and that sumoylation affects EXO1 ubiquitylation and protein stability. We identify an UBC9-PIAS1/PIAS4-dependent mechanism controlling human EXO1 sumoylation in vivo and demonstrate conservation of this mechanism in yeast by the Ubc9-Siz1/Siz2 using an in vitro reconstituted system. Furthermore, we show physical interaction between EXO1 and the de-sumoylating enzyme SENP6 both in vitro and in vivo, promoting EXO1 stability. Finally, we identify the major sites of sumoylation in EXO1 and show that ectopic expression of a sumoylation-deficient form of EXO1 rescues the DNA damage-induced chromosomal aberrations observed upon wt-EXO1 express

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cell Cycle

ISSN

1538-4101

e-ISSN

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Svazek periodika

14

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

2439-2450

Kód UT WoS článku

000359768900015

EID výsledku v databázi Scopus

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