Hyper-Acetylation of Histone H3K56 Limits Break-Induced Replication by Inhibiting Extensive Repair Synthesis


Chromatin poses a barrier to the recombination process. Chromatin modification is therefore a prerequisite factor for the efficient execution of the recombination event. Chromatin remodeling and several unique histone modifications at or near DNA double strand breaks (DSBs) facilitate early recombination processes, but little is known how chromatin state impinges on post-invasion steps of recombination, such as repair synthesis through homologous template, particularly recombination subtypes such as break-induced replication (BIR) involving extensive repair synthesis. Here, we investigated the effect of deletions in chromatin modification and remodeling genes on BIR and discovered that hyper-acetylation of H3K56 selectively impairs BIR and gene conversion associated with long DNA gap synthesis. We also found that hyper-acetylation of H3K56 interferes with the recovery from replication stress in checkpoint deficient cells and induces translocation-type gross chromosomal rearrangements (GCRs). The results provide a basic understanding of how histone modification facilitates efficient fork progression in recombination, controls the types of the repair products and sustains chromosome integrity upon induction of genotoxic stress.


Vyšlo v časopise: Hyper-Acetylation of Histone H3K56 Limits Break-Induced Replication by Inhibiting Extensive Repair Synthesis. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004990
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004990

Souhrn

Chromatin poses a barrier to the recombination process. Chromatin modification is therefore a prerequisite factor for the efficient execution of the recombination event. Chromatin remodeling and several unique histone modifications at or near DNA double strand breaks (DSBs) facilitate early recombination processes, but little is known how chromatin state impinges on post-invasion steps of recombination, such as repair synthesis through homologous template, particularly recombination subtypes such as break-induced replication (BIR) involving extensive repair synthesis. Here, we investigated the effect of deletions in chromatin modification and remodeling genes on BIR and discovered that hyper-acetylation of H3K56 selectively impairs BIR and gene conversion associated with long DNA gap synthesis. We also found that hyper-acetylation of H3K56 interferes with the recovery from replication stress in checkpoint deficient cells and induces translocation-type gross chromosomal rearrangements (GCRs). The results provide a basic understanding of how histone modification facilitates efficient fork progression in recombination, controls the types of the repair products and sustains chromosome integrity upon induction of genotoxic stress.


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