Parental histone distribution and location of the replication obstacle at nascent strands control homologous recombination

The advance and stability of replication forks rely on a tight co-regulation of DNA synthesis and nucleosome assembly. We show that mutants affected in parental histone recycling are impaired in the recombinational repair of the single-stranded DNA gaps generated in response to DNA adducts that hamper replication, which are then filled in by translesion synthesis. These recombination defects are in part due to an excess of parental nucleosomes at the invaded strand that destabilizes the sister chromatid junction formed after strand invasion through a Srs2-dependent mechanism. In addition, we show that a dCas9*/R-loop is more recombinogenic when the dCas9*/DNA-RNA hybrid interferes with the lagging than with the leading strand, and this recombination is particularly sensitive to problems in the deposition of parental histones at the strand that contains the hindrance. Therefore, parental histone distribution and location of the replication obstacle at the lagging or leading strand regulate homologous recombination.

Automated summary

The advance and stability of replication forks are regulated by the coordination of DNA synthesis and nucleosome assembly. Mutants with impaired parental histone recycling exhibit defects in recombinational repair of single-stranded DNA gaps generated during replication. These defects are caused by excessive parental nucleosomes at the invaded strand and interference with strand invasion via a Srs2-dependent mechanism. Additionally, the location of replication obstacles and distribution of parental histones regulate homologous recombination, with hindrance on the lagging strand showing greater sensitivity.