RT Journal Article
SR Electronic
T1 Chromatin modifiers alter recombination between divergent DNA sequences
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 519397
DO 10.1101/519397
A1 Ujani Chakraborty
A1 Beata Mackenroth
A1 Eric Alani
YR 2019
UL http://biorxiv.org/content/early/2019/01/13/519397.abstract
AB Recombination between divergent DNA sequences is actively prevented by heteroduplex rejection mechanisms. In baker’s yeast such anti-recombination mechanisms can be initiated by the recognition of DNA mismatches in heteroduplex DNA by MSH proteins, followed by recruitment of the Sgs1-Top3-Rmi1 helicase-topoisomerase complex to unwind the recombination intermediate. We previously showed that the repair/rejection decision during single-strand annealing recombination is temporally regulated by MSH protein levels and by factors that excise non-homologous single-stranded tails. These observations, coupled with recent studies indicating that mismatch repair factors interact with components of the histone chaperone machinery, encouraged us to explore roles for epigenetic factors and chromatin conformation in regulating the decision to reject vs. repair recombination between divergent DNA substrates. This work involved the use of an inverted repeat recombination assay thought to measure sister chromatid repair during DNA replication. Our observations are consistent with the histone chaperones CAF-1 and Rtt106 and the histone deacetylase Sir2 acting to suppress heteroduplex rejection and the Rpd3, Hst3 and Hst4 deacetylases acting to promote heteroduplex rejection. These observations and double mutant analysis have led to a model in which nucleosomes located at DNA lesions stabilize recombination intermediates and compete with mismatch repair factors that mediate heteroduplex rejection.