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

0582794 - ÚOCHB 2024 RIV US eng J - Článek v odborném periodiku
Ozgencil, M. - Dullovi, A. - Higos, R. C. C. - Hořejší, Zuzana - Bellelli, R.
The linker histone H1-BRCA1 axis is a crucial mediator of replication fork stability.
Life Science Alliance. Roč. 6, č. 9 (2023), č. článku e202301933. E-ISSN 2575-1077
Institucionální podpora: RVO:61388963
Klíčová slova: DNA replication * replication stress * linker histone
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.4, rok: 2022
Způsob publikování: Open access
https://doi.org/10.26508/lsa.202301933

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.
Trvalý link: https://hdl.handle.net/11104/0350845