The linker histone H1-BRCA1 axis is a crucial mediator of replication fork stability

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00582794" target="_blank" >RIV/61388963:_____/23:00582794 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.26508/lsa.202301933" target="_blank" >https://doi.org/10.26508/lsa.202301933</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.26508/lsa.202301933" target="_blank" >10.26508/lsa.202301933</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The linker histone H1-BRCA1 axis is a crucial mediator of replication fork stability

Popis výsledku v původním jazyce

The maintenance of genome integrity relies on replication fork stabilization upon encountering endogenous and exogenous sources of DNA damage. How this process is coordinated with the local chromatin environment remains poorly defined. Here, we show that the replication-dependent histone H1 variants interact with the tumour suppressor BRCA1 in a replication stress- dependent manner. Transient loss of the replication-dependent histones H1 does not affect fork progression in unchallenged conditions but leads to the accumulation of stalled replication intermediates. Upon challenge with hydroxyurea, cells deficient for histone H1 variants fail to recruit BRCA1 to stalled replication forks and undergo MRE11-dependent fork resection and collapse, which ultimately leads to genomic instability and cell death. In summary, our work defines an essential role of the replicationdependent histone H1 variants in mediating BRCA1-dependent fork protection and genome stability.

Název v anglickém jazyce

The linker histone H1-BRCA1 axis is a crucial mediator of replication fork stability

Popis výsledku anglicky

The maintenance of genome integrity relies on replication fork stabilization upon encountering endogenous and exogenous sources of DNA damage. How this process is coordinated with the local chromatin environment remains poorly defined. Here, we show that the replication-dependent histone H1 variants interact with the tumour suppressor BRCA1 in a replication stress- dependent manner. Transient loss of the replication-dependent histones H1 does not affect fork progression in unchallenged conditions but leads to the accumulation of stalled replication intermediates. Upon challenge with hydroxyurea, cells deficient for histone H1 variants fail to recruit BRCA1 to stalled replication forks and undergo MRE11-dependent fork resection and collapse, which ultimately leads to genomic instability and cell death. In summary, our work defines an essential role of the replicationdependent histone H1 variants in mediating BRCA1-dependent fork protection and genome stability.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Life Science Alliance

ISSN

2575-1077

e-ISSN

2575-1077

Svazek periodika

6

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

e202301933

Kód UT WoS článku

001022779800002

EID výsledku v databázi Scopus

2-s2.0-85163290315