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README.md

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 # RepProfs
+R functions used to build the replication profiles from CGS data.
 
-DNA polymerase epsilon (Polε) carries out leading strand synthesis with high fidelity owing to its exonuclease activity. Polε polymerase and exonuclease activities are in balance, due to partitioning of nascent strands between catalytic sites, so that net end resection occurs when synthesis is impaired. Stalling of chromosomal DNA synthesis activates replication checkpoint kinases, required to preserve the functional integrity of replication forks. We found that Polε is phosphorylated in a Rad53CHK1-dependent manner upon fork stalling, likely to limit Polε-driven nascent strand resection that causes replication fork collapse. In stress conditions Polε phosphorylation occurs on serine 430 of the Pol2 catalytic subunit. A S430 phosphomimic limits strand partitioning and exonucleolytic processivity, while non-phosphorylatable Pol2-S430A bypasses checkpoint regulation causing stalled fork resection and collapse. We propose that checkpoint kinases switch Polε to an exonuclease-safe mode by curbing active site partitioning thus preventing nascent strand resection and stabilizing stalled replication forks. 
+## Article
+Checkpoint-mediated DNA polymerase ε exonuclease activity curbing counteracts resection-driven fork collapse
+
+## Abstract
+DNA polymerase epsilon (Pole) carries out high fidelity leading strand synthesis owing to its exonuclease activity. Pole polymerase and exonuclease activities are balanced, due to partitioning of nascent DNA strands between catalytic sites, so that net resection occurs when synthesis is impaired. In vivo, DNA synthesis stalling activates replication checkpoint kinases, which act to preserve the functional integrity of replication forks. We show that stalled Pole drives nascent strand resection causing fork functional collapse, averted via checkpoint-dependent phosphorylation. Pole catalytic subunit Pol2 is phosphorylated on serine 430, influencing partitioning between polymerase and exonuclease active sites. A phosphormimetic S430D change reduces exonucleolysis in vitro and counteracts fork collapse. Conversely, non-phosphorylatable pol2-S430A expression causes resection-driven stressed fork defects. Our findings reveal that checkpoint kinases switch Pole to an exonuclease-safe mode preventing nascent strand resection and stabilizing stalled replication forks. Elective partitioning suppression has implications for the diverse Pole roles in genome integrity maintenance.