PT - JOURNAL ARTICLE AU - Amandine Batté AU - Sophie C van der Horst AU - Mireille Tittel-Elmer AU - Su Ming Sun AU - Sushma Sharma AU - Jolanda van Leeuwen AU - Andrei Chabes AU - Haico van Attikum 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 - https://www.life-science-alliance.org/content/5/4/e202101153.short 4100 - https://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.