Chl1 helicase controls replication fork progression by regulating dNTP pools.

Details

Serval ID
serval:BIB_388048BE3334
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Chl1 helicase controls replication fork progression by regulating dNTP pools.
Journal
Life science alliance
Author(s)
Batté A., van der Horst S.C., Tittel-Elmer M., Sun S.M., Sharma S., van Leeuwen J., Chabes A., van Attikum H.
ISSN
2575-1077 (Electronic)
ISSN-L
2575-1077
Publication state
Published
Issued date
04/2022
Peer-reviewed
Oui
Volume
5
Number
4
Pages
e202101153
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Eukaryotic cells have evolved a replication stress response that helps to overcome stalled/collapsed replication forks and ensure proper DNA replication. The replication checkpoint protein Mrc1 plays important roles in these processes, although its functional interactions are not fully understood. Here, we show that MRC1 negatively interacts with CHL1, which encodes the helicase protein Chl1, suggesting distinct roles for these factors during the replication stress response. Indeed, whereas Mrc1 is known to facilitate the restart of stalled replication forks, we uncovered that Chl1 controls replication fork rate under replication stress conditions. Chl1 loss leads to increased RNR1 gene expression and dNTP levels at the onset of S phase likely without activating the DNA damage response. This in turn impairs the formation of RPA-coated ssDNA and subsequent checkpoint activation. Thus, the Chl1 helicase affects RPA-dependent checkpoint activation in response to replication fork arrest by ensuring proper intracellular dNTP levels, thereby controlling replication fork progression under replication stress conditions.
Keywords
Cell Cycle Proteins/genetics, Cells, Cultured, Chromosomal Proteins, Non-Histone/genetics, DEAD-box RNA Helicases, DNA Helicases, DNA Replication/genetics, Deoxyribonucleotides/genetics, Deoxyribonucleotides/metabolism, Humans, Saccharomyces cerevisiae Proteins/genetics
Pubmed
Web of science
Open Access
Yes
Create date
14/01/2022 13:50
Last modification date
01/04/2022 6:35
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