减数分裂DNA断裂切除和重组依赖于染色质重塑器Fun30。

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI:10.1038/s44318-024-00318-8
Pei-Ching Huang, Soogil Hong, Hasan F Alnaser, Eleni P Mimitou, Keun P Kim, Hajime Murakami, Scott Keeney
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引用次数: 0

摘要

DNA双链断裂(DSBs)是通过核分解生成单链DNA进行同源重组的过程。在酿酒酵母减数分裂中,这种切除包括Mre11-Rad50-Xrs2复合体(MRX)的切口,然后由Exo1进行核外溶酶切。减数分裂DSBs的染色质重塑被认为是切除的必要条件,但重塑酶是未知的。在这里,我们发现SWI/ snf样atp酶Fun30在减数分裂切除中起着主要的、非冗余的作用。fun30突变缩短切除束的程度几乎与exo1- 2(核酸酶死亡)突变一样严重,并且在fun30 exo1- 2双突变中切除束进一步缩短。Fun30在对dsb的反应中与染色质相关,并且在缺乏Fun30的情况下,核小体的组成定位决定了切除终点的位置。我们推断Fun30促进了MRX和exo1依赖的切除步骤,可能是通过去除破碎染色单体上的核小体。此外,fun30 exo1和双突变体的极短切除伴随着同源间重组偏倚受损,导致重组和染色体分离缺陷。因此,这项研究也提供了对鲁棒重组所需的最小切除长度的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Meiotic DNA break resection and recombination rely on chromatin remodeler Fun30.

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.

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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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