The yeast proteases Ddi1 and Wss1 are both involved in the DNA replication stress response

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00509273" target="_blank" >RIV/61388963:_____/19:00509273 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/19:10399837

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S1568786419300874?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1568786419300874?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.dnarep.2019.06.008" target="_blank" >10.1016/j.dnarep.2019.06.008</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The yeast proteases Ddi1 and Wss1 are both involved in the DNA replication stress response

Popis výsledku v původním jazyce

Genome integrity and cell survival are dependent on proper replication stress response. Multiple repair pathways addressing obstacles generated by replication stress arose during evolution, and a detailed understanding of these processes is crucial for treatment of numerous human diseases. Here, we investigated the strong negative genetic interaction between two proteases involved in the DNA replication stress response, yeast Wss1 and Ddi1. While Wss1 proteolytically acts on DNA-protein crosslinks, mammalian DDI1 and DDI2 proteins remove RTF2 from stalled forks via a proposed proteasome shuttle hypothesis. We show that the double-deleted Delta ddi1, Delta wss1 yeast strain is hypersensitive to the replication drug hydroxyurea and that this phenotype can be complemented only by catalytically competent Ddi1 protease. Furthermore, our data show the key involvement of the helical domain preceding the Ddi1 protease domain in response to replication stress caused by hydroxyurea, offering the first suggestion of this domain's biological function. Overall, our study provides a basis for a novel dual protease-based mechanism enabling yeast cells to counteract DNA replication stress.

Název v anglickém jazyce

The yeast proteases Ddi1 and Wss1 are both involved in the DNA replication stress response

Popis výsledku anglicky

Genome integrity and cell survival are dependent on proper replication stress response. Multiple repair pathways addressing obstacles generated by replication stress arose during evolution, and a detailed understanding of these processes is crucial for treatment of numerous human diseases. Here, we investigated the strong negative genetic interaction between two proteases involved in the DNA replication stress response, yeast Wss1 and Ddi1. While Wss1 proteolytically acts on DNA-protein crosslinks, mammalian DDI1 and DDI2 proteins remove RTF2 from stalled forks via a proposed proteasome shuttle hypothesis. We show that the double-deleted Delta ddi1, Delta wss1 yeast strain is hypersensitive to the replication drug hydroxyurea and that this phenotype can be complemented only by catalytically competent Ddi1 protease. Furthermore, our data show the key involvement of the helical domain preceding the Ddi1 protease domain in response to replication stress caused by hydroxyurea, offering the first suggestion of this domain's biological function. Overall, our study provides a basis for a novel dual protease-based mechanism enabling yeast cells to counteract DNA replication stress.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

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

2019

Kód důvěrnosti údajů

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

Název periodika

Dna Repair

ISSN

1568-7864

e-ISSN

—

Svazek periodika

80

Číslo periodika v rámci svazku

Aug

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

7

Strana od-do

45-51

Kód UT WoS článku

000485852000006

EID výsledku v databázi Scopus

2-s2.0-85068171912