The BLM helicase has been shown to maintain genome stability by preventing accumulation of aberrant recombination intermediates. We show here that the Saccharomyces cerevisiae BLM ortholog, Sgs1, plays an integral role in normal meiotic recombination, beyond its documented activity limiting aberrant recombination intermediates. In wild-type meiosis, temporally and mechanistically distinct pathways produce crossover and noncrossover recombinants. Crossovers form late in meiosis I prophase, by polo kinase-triggered resolution of Holliday junction (HJ) intermediates. Noncrossovers form earlier, via processes that do not involve stable HJ intermediates. In contrast, sgs1 mutants abolish early noncrossover formation. Instead, both noncrossovers and crossovers form by late HJ intermediate resolution, using an alternate pathway requiring the overlapping activities of Mus81-Mms4, Yen1, and Slx1-Slx4, nucleases with minor roles in wild-type meiosis. We conclude that Sgs1 is a primary regulator of recombination pathway choice during meiosis and suggest a similar function in the mitotic cell cycle.
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http://dx.doi.org/10.1016/j.molcel.2012.02.020 | DOI Listing |
Methods Mol Biol
December 2024
Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.
Homologous recombination (HR) is the principal pathway undertaken by a cell for the error-free repair of DNA double-strand breaks that are frequently encountered by the cell. HR can be initiated at the sites of DNA double-strand breaks by generating long stretches of single-stranded 3' DNA overhang through a process called DNA end resection. In one DNA end resection pathway, this is achieved via the concerted effort of specialized machinery involving the RecQ family helicase BLM, the helicase/endonuclease DNA2, and a single-strand DNA binding protein complex RPA.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
Incomplete sister centromere decatenation results in centromeric ultrafine anaphase bridges (UFBs). PICH (PLK1-interacting checkpoint helicase), a DNA translocase, plays a crucial role in UFB resolution by recruiting UFB-binding proteins and stimulating topoisomerase IIα. However, the involvement of distinct PICH functions in UFB resolution remains ambiguous.
View Article and Find Full Text PDFPLoS Genet
December 2024
Department of Microbiology & Immunology, W. R. Hearst Microbiology Research Center, Weill Cornell Medicine, New York, New York, United States of America.
TRF2 is an essential and conserved double-strand telomere binding protein that stabilizes chromosome ends by suppressing DNA damage response and aberrant DNA repair. Herein we investigated the mechanisms and functions of the Trf2 ortholog in the basidiomycete fungus Ustilago maydis, which manifests strong resemblances to metazoans with regards to the telomere and DNA repair machinery. We showed that UmTrf2 binds to Blm in vitro and inhibits Blm-mediated unwinding of telomeric DNA substrates.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Graduate School of Integrated Sciences for Life, Hiroshima University, Japan. Electronic address:
Homologous recombination is vital for DNA double-strand break repair. Dysfunction in homologous recombination can lead to cell death, mutations, and cancer. In fission yeast (Schizosaccharomyces pombe), RecQ helicase Rqh1 resolves recombination intermediates.
View Article and Find Full Text PDFSci Rep
October 2024
Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Life Sciences, Guizhou University, Guiyang, 550025, China.
To determine the synergistic effect and mechanism of AO/854, a new Bloom syndrome protein (BLM) helicase inhibitor, and cisplatin (CDDP), a DNA-crosslinking agent, cell viability assays, neutral comet assays, and Western blotting (WB) were performed on prostate cancer (PCa) cells. According to our findings, combining AO/854 and CDDP enhanced the antiproliferative capabilities of PC3 cell lines. As evidenced by the upregulation of γH2AX, cleaved caspase-3/caspase-3, and BAX/Bcl-2, AO/854 dramatically increased PC3 apoptosis and DNA damage induced by CDDP.
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