RRC ID 59296
Author Onaka AT, Su J, Katahira Y, Tang C, Zafar F, Aoki K, Kagawa W, Niki H, Iwasaki H, Nakagawa T.
Title DNA replication machinery prevents Rad52-dependent single-strand annealing that leads to gross chromosomal rearrangements at centromeres.
Journal Commun Biol
Abstract Homologous recombination between repetitive sequences can lead to gross chromosomal rearrangements (GCRs). At fission yeast centromeres, Rad51-dependent conservative recombination predominantly occurs between inverted repeats, thereby suppressing formation of isochromosomes whose arms are mirror images. However, it is unclear how GCRs occur in the absence of Rad51 and how GCRs are prevented at centromeres. Here, we show that homology-mediated GCRs occur through Rad52-dependent single-strand annealing (SSA). The rad52-R45K mutation, which impairs SSA activity of Rad52 protein, dramatically reduces isochromosome formation in rad51 deletion cells. A ring-like complex Msh2-Msh3 and a structure-specific endonuclease Mus81 function in the Rad52-dependent GCR pathway. Remarkably, mutations in replication fork components, including DNA polymerase α and Swi1/Tof1/Timeless, change the balance between Rad51-dependent recombination and Rad52-dependent SSA at centromeres, increasing Rad52-dependent SSA that forms isochromosomes. Our results uncover a role of DNA replication machinery in the recombination pathway choice that prevents Rad52-dependent GCRs at centromeres.
Volume 3(1)
Pages 202
Published 2020-4-30
DOI 10.1038/s42003-020-0934-0
PII 10.1038/s42003-020-0934-0
PMID 32355220
PMC PMC7193609
MeSH Centromere / genetics* DNA Replication* Gene Rearrangement* Rad52 DNA Repair and Recombination Protein / genetics* Rad52 DNA Repair and Recombination Protein / metabolism Saccharomyces cerevisiae Proteins / genetics* Saccharomyces cerevisiae Proteins / metabolism Schizosaccharomyces / genetics*
IF 4.165
Times Cited 0