Cohesin regulates homology search during recombinational DNA repair

被引：52

作者：

Piazza, Aurele ^{[1
,2
]}

Bordelet, Helene ^{[1
,2
]}

Dumont, Agnes ^{[2
]}

Thierry, Agnes ^{[1
]}

Savocco, Jerome ^{[2
]}

Girard, Fabien ^{[1
]}

Koszul, Romain ^{[1
]}

机构：

[1] Inst Pasteur, Unite Regulat Spatiale Genomes, CNRS UMR3525, F-75015 Paris, France

[2] Univ Lyon, ENS Lyon, Lab Biol & Modelisat Cellule, Univ Claude Bernard,CNRS UMR5239,INSERM U1210, 46 Allee Italie, F-69007 Lyon, France

来源：

NATURE CELL BIOLOGY | 2021年 / 23卷 / 11期

基金：

欧洲研究理事会;

关键词：

DOUBLE-STRAND-BREAK; SISTER-CHROMATID COHESION; GENE CONVERSION; DAMAGE RESPONSE; READ ALIGNMENT; MECHANISM; CHROMOSOMES; ARCHITECTURE; CHECKPOINT; ADAPTATION;

D O I：

10.1038/s41556-021-00783-x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Homologous recombination repairs DNA double-strand breaks (DSB) using an intact dsDNA molecule as a template. It entails a homology search step, carried out along a conserved RecA/Rad51-ssDNA filament assembled on each DSB end. Whether, how and to what extent a DSB impacts chromatin folding, and how this (re)organization in turns influences the homology search process, remain ill-defined. Here we characterize two layers of spatial chromatin reorganization following DSB formation in Saccharomyces cerevisiae. Although cohesin folds chromosomes into cohesive arrays of similar to 20-kb-long chromatin loops as cells arrest in G2/M, the DSB-flanking regions interact locally in a resection- and 9-1-1 clamp-dependent manner, independently of cohesin, Mec1(ATR), Rad52 and Rad51. This local structure blocks cohesin progression, constraining the DSB region at the base of a loop. Functionally, cohesin promotes DSB-dsDNA interactions and donor identification in cis, while inhibiting them in trans. This study identifies multiple direct and indirect ways by which cohesin regulates homology search during recombinational DNA repair.

引用

页码：1176 / +

页数：30

共 87 条

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