Parental histone distribution at nascent strands controls homologous recombination during DNA damage tolerance

Abstract

The advance and stability of replication forks rely on a tight co-regulation of the processes of DNA synthesis and nucleosome assembly. We have addressed the relevance of parental histone recycling in the mechanisms of DNA damage tolerance (DDT) - homologous recombination (HR) and translesion synthesis (TLS) - that assist replication forks under conditions that block their advance. We show that mutants affected in the deposition of parental histones are impaired in the recombinational repair of the single-strand DNA gaps generated during DDT, with the defects being more severe in mutants impaired in the lagging strand-specific deposition pathway. These recombinational defects are not due to a deficit of parental histones at the nascent strands but to an excess of parental nucleosomes at the invaded strand that destabilizes the sister chromatid junction formed after strand invasion. In conclusion, parental histone distribution at stressed forks regulates HR and provides a potential mechanism for the choice between HR and TLS that would depend on whether DNA synthesis is blocked at the lagging or the leading strand.