Meiotic DNA break resection and recombination rely on chromatin remodeler Fun30 Journal Article
| Authors: | Huang, P. C.; Hong, S.; Alnaser, H. F.; Mimitou, E. P.; Kim, K. P.; Murakami, H.; Keeney, S. |
| Article Title: | Meiotic DNA break resection and recombination rely on chromatin remodeler Fun30 |
| Abstract: | DNA double-strand breaks (DSBs) are nucleolytically processed to generate single-stranded DNA for homologous recombination. In Saccharomyces cerevisiae meiosis, this resection involves nicking by the Mre11–Rad50–Xrs2 complex (MRX), then exonucleolytic digestion by Exo1. Chromatin remodeling at meiotic DSBs is thought necessary for resection, but the remodeling enzyme was unknown. Here we show that the SWI/SNF-like ATPase Fun30 plays a major, nonredundant role in meiotic resection. A fun30 mutation shortened resection tracts almost as severely as an exo1-nd (nuclease-dead) mutation, and resection was further shortened in a fun30 exo1-nd double mutant. Fun30 associates with chromatin in response to DSBs, and the constitutive positioning of nucleosomes governs resection endpoint locations in the absence of Fun30. We infer that Fun30 promotes both the MRX- and Exo1-dependent steps in resection, possibly by removing nucleosomes from broken chromatids. Moreover, the extremely short resection in fun30 exo1-nd double mutants is accompanied by compromised interhomolog recombination bias, leading to defects in recombination and chromosome segregation. Thus, this study also provides insight about the minimal resection lengths needed for robust recombination. © The Author(s) 2024. |
| Keywords: | controlled study; unclassified drug; gene mutation; sequence analysis; genetics; mutation; nonhuman; polymerase chain reaction; meiosis; metabolism; gene; homologous recombination; dna repair; transcription factor; assay; transcription factors; genetic recombination; saccharomyces cerevisiae; recombination, genetic; dna breaks, double-stranded; double stranded dna break; resection; saccharomyces cerevisiae proteins; saccharomyces cerevisiae protein; bioinformatics; adenosine triphosphatase; fluorescence activated cell sorting; chromatin assembly and disassembly; chromosome segregation; chromatin structure; prophase; chromosome 7; exodeoxyribonuclease; exodeoxyribonucleases; recombination; crossing over; nucleosome; nucleosomes; dna isolation; southern blotting; restriction fragment length polymorphism; peptides and proteins; sporogenesis; article; spore viability; fungal viability; exo1; chromatin immunoprecipitation sequencing; k means clustering; lethal mutation; fun30; cct6 protein; chromatin remodeler fun30; exo1 protein; gaba transporter 1; exodeoxyribonuclease i; fun30 protein, s cerevisiae; arg4 gene; bud23 gene; cys3 gene; dna break resection; erg1 gene; s1-seq; spore-autonomous fluorescent reporter assay |
| Journal Title: | EMBO Journal |
| Volume: | 44 |
| Issue: | 1 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2025-01-02 |
| Start Page: | 200 |
| End Page: | 224 |
| Language: | English |
| DOI: | 10.1038/s44318-024-00318-8 |
| PUBMED: | 39613969 |
| PROVIDER: | scopus |
| PMCID: | PMC11695836 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Scott Keeney -- Source: Scopus |
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