Histone deposition promotes recombination-dependent replication at arrested forks

Autoři: Julien Hardy aff001;  Dingli Dai aff001;  Anissia Ait Saada aff001;  Ana Teixeira-Silva aff001;  Louise Dupoiron aff001;  Fatemeh Mojallali aff001;  Karine Fréon aff001;  Francoise Ochsenbein aff004;  Brigitte Hartmann aff005;  Sarah Lambert aff001
Působiště autorů: Institut Curie, PSL Research University, UMR3348, Orsay, France aff001;  University Paris Sud, Paris-Saclay University, UMR3348, Orsay, France aff002;  CNRS, UMR3348, Orsay France aff003;  CEA, DRF, SB2SM, Laboratoire de Biologie Structurale et Radiobiologie, Gif-sur-Yvette, France aff004;  Laboratoire de Biologie et Pharmacologie Appliquée (LBPA) UMR 8113, CNRS / ENS de Cachan, Cachan cedex, France aff005
Vyšlo v časopise: Histone deposition promotes recombination-dependent replication at arrested forks. PLoS Genet 15(10): e32767. doi:10.1371/journal.pgen.1008441
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008441


Replication stress poses a serious threat to genome stability. Recombination-Dependent-Replication (RDR) promotes DNA synthesis resumption from arrested forks. Despite the identification of chromatin restoration pathways after DNA repair, crosstalk coupling RDR and chromatin assembly is largely unexplored. The fission yeast Chromatin Assembly Factor-1, CAF-1, is known to promote RDR. Here, we addressed the contribution of histone deposition to RDR. We expressed a mutated histone, H3-H113D, to genetically alter replication-dependent chromatin assembly by destabilizing (H3-H4)2 tetramer. We established that DNA synthesis-dependent histone deposition, by CAF-1 and Asf1, promotes RDR by preventing Rqh1-mediated disassembly of joint-molecules. The recombination factor Rad52 promotes CAF-1 binding to sites of recombination-dependent DNA synthesis, indicating that histone deposition occurs downstream Rad52. Histone deposition and Rqh1 activity act synergistically to promote cell resistance to camptothecin, a topoisomerase I inhibitor that induces replication stress. Moreover, histone deposition favors non conservative recombination events occurring spontaneously in the absence of Rqh1, indicating that the stabilization of joint-molecules by histone deposition also occurs independently of Rqh1 activity. These results indicate that histone deposition plays an active role in promoting RDR, a benefit counterbalanced by stabilizing at-risk joint-molecules for genome stability.

Klíčová slova:

DNA repair – DNA replication – DNA synthesis – Histones – Chromatin – Saccharomyces cerevisiae – Schizosaccharomyces pombe – Nucleosomes


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