RT Journal Article
SR Electronic
T1 Chl1 helicase controls replication fork progression by regulating dNTP pools
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101153
DO 10.26508/lsa.202101153
VO 5
IS 4
A1 Amandine Batté
A1 Sophie C van der Horst
A1 Mireille Tittel-Elmer
A1 Su Ming Sun
A1 Sushma Sharma
A1 Jolanda van Leeuwen
A1 Andrei Chabes
A1 Haico van Attikum
YR 2022
UL https://www.life-science-alliance.org/content/5/4/e202101153.abstract
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.