PT  - JOURNAL ARTICLE
AU  - Batté, Amandine
AU  - van der Horst, Sophie C
AU  - Tittel-Elmer, Mireille
AU  - Sun, Su Ming
AU  - Sharma, Sushma
AU  - van Leeuwen, Jolanda
AU  - Chabes, Andrei
AU  - van Attikum, Haico
TI  - Chl1 helicase controls replication fork progression by regulating dNTP pools
AID  - 10.26508/lsa.202101153
DP  - 2022 Apr 01
TA  - Life Science Alliance
PG  - e202101153
VI  - 5
IP  - 4
4099  - http://www.life-science-alliance.org/content/5/4/e202101153.short
4100  - http://www.life-science-alliance.org/content/5/4/e202101153.full
SO  - Life Sci. Alliance2022 Apr 01; 5
AB  - 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.