H2B Mono-ubiquitylation Facilitates Fork Stalling and Recovery during Replication Stress by Coordinating Rad53 Activation and Chromatin Assembly

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Eukaryotic DNA is organized into nucleosomes, which are the fundamental repeating units of chromatin. Coordination of chromatin structure is required for efficient and accurate DNA replication. Aberrant DNA replication results in mutations and chromosome rearrangements that may be associated with human disorders. Therefore, cellular surveillance mechanisms have evolved to counteract potential threats to DNA replication. These mechanisms include checkpoints and specialized enzymatic activities that prevent the replication and segregation of defective DNA molecules. We employed a genome-wide approach to investigate how chromatin structure affects DNA replication under stress. We report that coordination of chromatin assembly and checkpoint activity by a histone modification, H2B ubiquitylation (H2Bub), is critical for the cell response to HU-induced replication stress. In cells with a mutation that abolishes H2Bub, replication progression is enhanced, and the forks are more susceptible to damage by environmental insults. The replication proteins on replicating DNA are akin to a train on the tracks, and movement of this train is carefully controlled. Our data indicate that H2Bub helps organize DNA in the nuclei during DNA replication; this process plays a similar role to the brakes on a train, serving to slow down replication, and maintaining stable progression of replication under environmental stress.

Vyšlo v časopise: H2B Mono-ubiquitylation Facilitates Fork Stalling and Recovery during Replication Stress by Coordinating Rad53 Activation and Chromatin Assembly. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004667
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004667

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