RT Journal Article
SR Electronic
T1 Srs2 helicase prevents the formation of toxic DNA damage during late prophase I of yeast meiosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 518035
DO 10.1101/518035
A1 Hiroyuki Sasanuma
A1 Hana Subhan M. Sakurai
A1 Yuko Furihata
A1 Kiran Challa
A1 Lira Palmer
A1 Susan M. Gasser
A1 Miki Shinohara
A1 Akira Shinohara
YR 2019
UL http://biorxiv.org/content/early/2019/01/11/518035.abstract
AB Proper repair of double-strand breaks (DSBs) is key to ensure proper chromosome segregation. In this study, we found that the deletion of the SRS2 gene, which encodes a DNA helicase necessary for the control of homologous recombination, induces aberrant chromosome segregation during budding yeast meiosis. This abnormal chromosome segregation in srs2 cells accompanies the formation of a novel DNA damage induced during late meiotic prophase-I. The damage may contain long stretches of single-stranded DNAs (ssDNAs), which lead to aggregate formation of a ssDNA binding protein, RPA, and a RecA homolog, Rad51, as well as other recombination proteins inside of the nuclei. The Rad51 aggregate formation in the srs2 mutant depends on the initiation of meiotic recombination and occurs in the absence of chromosome segregation. Importantly, as an early recombination intermediate, we detected a thin bridge of Rad51 between two Rad51 foci or among the foci in the srs2 mutant, which is rarely seen in wild type. These might be cytological manifestation of the connection of two DSB ends and multi-invasion. The DNA damage with Rad51 aggregates in the srs2 mutant is passed through anaphase-I and -II, suggesting the absence of DNA damage-induced cell-cycle arrest after the pachytene stage. We propose that Srs2 helicase resolves early protein-DNA recombination intermediates to suppress the formation of aberrant lethal DNA damage during late prophase-I.