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Smc5/6 与 Sgs1-Top3-Rmi1 一起作用,在天然停顿位点完成染色体复制。

Smc5/6 functions with Sgs1-Top3-Rmi1 to complete chromosome replication at natural pause sites.

机构信息

IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy.

Institute for Cancer Genetics, Department of Pathology and Cell Biology, College of Physicians & Surgeons, Columbia University, New York, NY, USA.

出版信息

Nat Commun. 2021 Apr 8;12(1):2111. doi: 10.1038/s41467-021-22217-w.


DOI:10.1038/s41467-021-22217-w
PMID:33833229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8032827/
Abstract

Smc5/6 is essential for genome structural integrity by yet unknown mechanisms. Here we find that Smc5/6 co-localizes with the DNA crossed-strand processing complex Sgs1-Top3-Rmi1 (STR) at genomic regions known as natural pausing sites (NPSs) where it facilitates Top3 retention. Individual depletions of STR subunits and Smc5/6 cause similar accumulation of joint molecules (JMs) composed of reversed forks, double Holliday Junctions and hemicatenanes, indicative of Smc5/6 regulating Sgs1 and Top3 DNA processing activities. We isolate an intra-allelic suppressor of smc6-56 proficient in Top3 retention but affected in pathways that act complementarily with Sgs1 and Top3 to resolve JMs arising at replication termination. Upon replication stress, the smc6-56 suppressor requires STR and Mus81-Mms4 functions for recovery, but not Srs2 and Mph1 helicases that prevent maturation of recombination intermediates. Thus, Smc5/6 functions jointly with Top3 and STR to mediate replication completion and influences the function of other DNA crossed-strand processing enzymes at NPSs.

摘要

Smc5/6 通过未知机制对基因组结构完整性至关重要。在这里,我们发现 Smc5/6 与 DNA 交叉链处理复合物 Sgs1-Top3-Rmi1(STR)在称为自然暂停位点(NPS)的基因组区域共定位,在该区域它促进 Top3 的保留。STR 亚基和 Smc5/6 的单独缺失会导致由反转叉、双 Holliday 连接和半侧链组成的连接分子(JMs)的类似积累,表明 Smc5/6 调节 Sgs1 和 Top3 的 DNA 处理活性。我们分离了一个等位基因内的抑制子 smc6-56,它在保留 Top3 方面很有效,但在与 Sgs1 和 Top3 互补的途径中受到影响,以解决在复制终止时出现的 JMs。在复制应激下,smc6-56 抑制子需要 STR 和 Mus81-Mms4 功能才能恢复,但不需要 Srs2 和 Mph1 解旋酶来防止重组中间体的成熟。因此,Smc5/6 与 Top3 和 STR 共同作用以介导复制完成,并影响 NPS 处其他 DNA 交叉链处理酶的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/eeff36806d88/41467_2021_22217_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/ee2b32c8518c/41467_2021_22217_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/2b1933d1aeb8/41467_2021_22217_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/332b2afc7911/41467_2021_22217_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/0b67708569ca/41467_2021_22217_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/20787c3fd5df/41467_2021_22217_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/74690dc10a57/41467_2021_22217_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/f8bf2d4427fe/41467_2021_22217_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/eeff36806d88/41467_2021_22217_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/ee2b32c8518c/41467_2021_22217_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/2b1933d1aeb8/41467_2021_22217_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/332b2afc7911/41467_2021_22217_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/0b67708569ca/41467_2021_22217_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/20787c3fd5df/41467_2021_22217_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/74690dc10a57/41467_2021_22217_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/f8bf2d4427fe/41467_2021_22217_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b7/8032827/eeff36806d88/41467_2021_22217_Fig8_HTML.jpg

相似文献

[1]
Smc5/6 functions with Sgs1-Top3-Rmi1 to complete chromosome replication at natural pause sites.

Nat Commun. 2021-4-8

[2]
Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates.

Cell Rep. 2016-7-12

[3]
Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination intermediates.

Mol Cell. 2013-10-10

[4]
Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6.

Genes Dev. 2016-6-1

[5]
Processing of homologous recombination repair intermediates by the Sgs1-Top3-Rmi1 and Mus81-Mms4 complexes.

Cell Cycle. 2011-9-15

[6]
Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease.

Genes Dev. 2001-10-15

[7]
Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex.

Mol Cell Biol. 2005-6

[8]
Top3-Rmi1 DNA single-strand decatenase is integral to the formation and resolution of meiotic recombination intermediates.

Mol Cell. 2015-2-19

[9]
Cooperativity of Mus81.Mms4 with Rad54 in the resolution of recombination and replication intermediates.

J Biol Chem. 2009-3-20

[10]
Smc5/6 complex regulates Sgs1 recombination functions.

Curr Genet. 2017-6

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[2]
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EMBO J. 2024-8

[3]
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J Clin Invest. 2024-3-26

[4]
The SMC5/6 complex: folding chromosomes back into shape when genomes take a break.

Nucleic Acids Res. 2024-3-21

[5]
SMC5/6 Promotes Replication Fork Stability via Negative Regulation of the COP9 Signalosome.

Int J Mol Sci. 2024-1-12

[6]
Large-scale phenogenomic analysis of human cancers uncovers frequent alterations affecting SMC5/6 complex components in breast cancer.

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[7]
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[8]
Genome control by SMC complexes.

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[9]
The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication centers.

Elife. 2022-11-14

[10]
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本文引用的文献

[1]
Purified Smc5/6 Complex Exhibits DNA Substrate Recognition and Compaction.

Mol Cell. 2020-12-17

[2]
The Smc5/6 Core Complex Is a Structure-Specific DNA Binding and Compacting Machine.

Mol Cell. 2020-12-17

[3]
SMC5/6 is required for replication fork stability and faithful chromosome segregation during neurogenesis.

Elife. 2020-11-17

[4]
SMC5/6 acts jointly with Fanconi anemia factors to support DNA repair and genome stability.

EMBO Rep. 2020-2-5

[5]
Dynamic Processing of Displacement Loops during Recombinational DNA Repair.

Mol Cell. 2019-3-21

[6]
Rescue of collapsed replication forks is dependent on NSMCE2 to prevent mitotic DNA damage.

PLoS Genet. 2019-2-8

[7]
The Smc5/6 Complex: New and Old Functions of the Enigmatic Long-Distance Relative.

Annu Rev Genet. 2018-11-23

[8]
The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects.

Nat Commun. 2018-9-11

[9]
Acute Smc5/6 depletion reveals its primary role in rDNA replication by restraining recombination at fork pausing sites.

PLoS Genet. 2018-1-23

[10]
Building up and breaking down: mechanisms controlling recombination during replication.

Crit Rev Biochem Mol Biol. 2017-3-22

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