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核架构对双链断裂修复效率的影响。

Effect of nuclear architecture on the efficiency of double-strand break repair.

机构信息

Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.

出版信息

Nat Cell Biol. 2013 Jun;15(6):694-9. doi: 10.1038/ncb2745. Epub 2013 May 5.


DOI:10.1038/ncb2745
PMID:23644470
Abstract

The most dangerous insults to the genome's integrity are those that break both strands of the DNA. Double-strand breaks can be repaired by homologous recombination; in this conserved mechanism, a global genomic homology search finds sequences similar to those near the break, and uses them as a template for DNA synthesis and ligation. Chromosomes occupy restricted territories within the nucleus. We show that yeast genomic regions whose nuclear territories overlap recombine more efficiently than sequences located in spatially distant territories. Tethering of telomeres and centromeres reduces the efficiency of recombination between distant genomic loci, lowering the chances of non-allelic recombination. Our results challenge present models that posit an active scanning of the whole nuclear volume by the broken chromosomal end; they demonstrate that the search for homology is a limiting step in homologous recombination, and emphasize the importance of nuclear organization in genome maintenance.

摘要

对基因组完整性最危险的威胁是那些同时破坏 DNA 双链的因素。双链断裂可以通过同源重组来修复;在这个保守的机制中,一个全局基因组同源搜索会找到与断裂附近相似的序列,并将其用作 DNA 合成和连接的模板。染色体在核内占据受限的领土。我们表明,核区重叠的酵母基因组区域比位于空间上遥远的区域的序列更有效地进行重组。端粒和着丝粒的连接降低了远距离基因组位点之间非等位重组的效率,降低了非等位重组的可能性。我们的结果挑战了目前的模型,该模型假设断裂染色体末端主动扫描整个核体积;它们表明同源搜索是同源重组的限制步骤,并强调了核组织在基因组维护中的重要性。

相似文献

[1]
Effect of nuclear architecture on the efficiency of double-strand break repair.

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[2]
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[3]
Increased chromosome mobility facilitates homology search during recombination.

Nat Cell Biol. 2012-4-8

[4]
Mdt1 facilitates efficient repair of blocked DNA double-strand breaks and recombinational maintenance of telomeres.

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[5]
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[6]
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[7]
Two different types of double-strand breaks in Saccharomyces cerevisiae are repaired by similar RAD52-independent, nonhomologous recombination events.

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[8]
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Methods Enzymol. 2018

[9]
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Adv Genet. 2002

[10]
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Genes Dev. 2009-2-1

引用本文的文献

[1]
Formation of chromosomal rearrangements in diploids through regionally-biased non-allelic homologous recombination.

bioRxiv. 2025-5-10

[2]
The Causes for Genomic Instability and How to Try and Reduce Them Through Rational Design of Synthetic DNA.

Methods Mol Biol. 2024

[3]
Polymer Modeling Reveals Interplay between Physical Properties of Chromosomal DNA and the Size and Distribution of Condensin-Based Chromatin Loops.

Genes (Basel). 2023-12-9

[4]
Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function.

Cell Genom. 2023-11-9

[5]
In vivo tracking of functionally tagged Rad51 unveils a robust strategy of homology search.

Nat Struct Mol Biol. 2023-10

[6]
Long-range DNA end resection supports homologous recombination by checkpoint activation rather than extensive homology generation.

Elife. 2023-6-30

[7]
Function and Evolution of the Loop Extrusion Machinery in Animals.

Int J Mol Sci. 2023-3-6

[8]
Repair Foci as Liquid Phase Separation: Evidence and Limitations.

Genes (Basel). 2022-10-13

[9]
Global chromatin mobility induced by a DSB is dictated by chromosomal conformation and defines the HR outcome.

Elife. 2022-9-20

[10]
Mechanisms of DNA Mobilization and Sequestration.

Genes (Basel). 2022-2-16

本文引用的文献

[1]
A predictive computational model of the dynamic 3D interphase yeast nucleus.

Curr Biol. 2012-8-30

[2]
Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery.

Nat Cell Biol. 2012-4-8

[3]
Increased chromosome mobility facilitates homology search during recombination.

Nat Cell Biol. 2012-4-8

[4]
Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination.

Genes Dev. 2012-2-15

[5]
Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search.

Nature. 2012-2-8

[6]
Genome architectures revealed by tethered chromosome conformation capture and population-based modeling.

Nat Biotechnol. 2011-12-25

[7]
High order chromatin architecture shapes the landscape of chromosomal alterations in cancer.

Nat Biotechnol. 2011-11-20

[8]
The replication checkpoint protects fork stability by releasing transcribed genes from nuclear pores.

Cell. 2011-7-22

[9]
KAP-1 phosphorylation regulates CHD3 nucleosome remodeling during the DNA double-strand break response.

Nat Struct Mol Biol. 2011-6-5

[10]
Principles of chromosomal organization: lessons from yeast.

J Cell Biol. 2011-3-7

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