Replication fork stalling elicits chromatin compaction for the stability of stalling replication forks

Abstract

Significance Stalling replication forks require strict cellular regulations for their stability. The intra-S phase checkpoint has been demonstrated essential for preventing stalling/stalled replication forks from collapse. In this study, a cellular pathway was uncovered that regulates the stabilization of stalling replication forks. We found that, when replication forks stall, the chromatin surrounding stalling forks becomes compacted. The fork stalling-induced chromatin compaction is achieved by modification changes on nucleosome histones, including H2BK33 deacetylation and H3K9 trimethylations. The experimental evidence further indicated that the replication fork stalling-induced chromatin compaction prevents the separation of the replicative helicase CMG and DNA polymerases, thus stabilizing stalling replication forks. This regulation pathway is named the “chromsfork” control: chromatin compaction stabilizes stalling replication forks.