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多种途径在端粒处抑制非同源末端连接。

Multiple pathways inhibit NHEJ at telomeres.

作者信息

Marcand Stéphane, Pardo Benjamin, Gratias Ariane, Cahun Sabrina, Callebaut Isabelle

机构信息

Centre National de la Recherche Scientifque UMR 217, Institut de Radiobiologie Cellulaire et Moléculaire, CEA/Fontenay, 92265 Fontenay-aux-roses cedex, France.

出版信息

Genes Dev. 2008 May 1;22(9):1153-8. doi: 10.1101/gad.455108.

DOI:10.1101/gad.455108
PMID:18451106
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2335312/
Abstract

The nonhomologous end-joining (NHEJ) repair pathway is inhibited at telomeres, preventing chromosome fusion. In budding yeast Saccharomyces cerevisiae, the Rap1 protein directly binds the telomere sequences and is required for NHEJ inhibition. Here we show that the Rap1 C-terminal domain establishes two parallel inhibitory pathways through the proteins Rif2 and Sir4. In addition, the central domain of Rap1 inhibits NHEJ independently of Rif2 and Sir4. Thus, Rap1 establishes several independent pathways to prevent telomere fusions. We discuss a possible mechanism that would explain Rif2 multifunctionality at telomeres and the recent evolutionary origin of Rif2 from an origin recognition complex (ORC) subunit.

摘要

非同源末端连接（NHEJ）修复途径在端粒处受到抑制，从而防止染色体融合。在芽殖酵母酿酒酵母中，Rap1蛋白直接结合端粒序列，是NHEJ抑制所必需的。在这里，我们表明Rap1的C末端结构域通过Rif2和Sir4蛋白建立了两条平行的抑制途径。此外，Rap1的中央结构域独立于Rif2和Sir4抑制NHEJ。因此，Rap1建立了几个独立的途径来防止端粒融合。我们讨论了一种可能的机制，该机制可以解释Rif2在端粒处的多功能性以及Rif2从起源识别复合物（ORC）亚基的近期进化起源。

相似文献

[1]
Multiple pathways inhibit NHEJ at telomeres.

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[2]
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[3]
Structural and functional studies of the Rap1 C-terminus reveal novel separation-of-function mutants.

J Mol Biol. 2008-7-11

[4]
Rif2 protects Rap1-depleted telomeres from MRX-mediated degradation in .

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[5]
Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends.

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[6]
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Curr Genet. 2021-2

[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Restriction of Ku translocation protects telomere ends.

Nat Commun. 2025-7-24

[2]
Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres.

Nucleic Acids Res. 2024-7-22

[3]
Unwrap RAP1's Mystery at Kinetoplastid Telomeres.

Biomolecules. 2024-1-4

[4]
Rif2 interaction with Rad50 counteracts Tel1 functions in checkpoint signalling and DNA tethering by releasing Tel1 from MRX binding.

Nucleic Acids Res. 2024-3-21

[5]
The increase in cell death rates in caloric restricted cells of the yeast helicase mutant rrm3 is Sir complex dependent.

Sci Rep. 2023-10-19

[6]
To Fix or Not to Fix: Maintenance of Chromosome Ends Versus Repair of DNA Double-Strand Breaks.

Cells. 2022-10-14

[7]
Rap1 prevents fusions between long telomeres in fission yeast.

EMBO J. 2022-10-17

[8]
DNA Damage Response-Associated Cell Cycle Re-Entry and Neuronal Senescence in Brain Aging and Alzheimer's Disease.

J Alzheimers Dis. 2023

[9]
Rif2 protects Rap1-depleted telomeres from MRX-mediated degradation in .

Elife. 2022-1-19

[10]
Sir3 heterochromatin protein promotes non-homologous end joining by direct inhibition of Sae2.

EMBO J. 2022-1-4

本文引用的文献

[1]
The origin recognition complex localizes to telomere repeats and prevents telomere-circle formation.

Curr Biol. 2007-11-20

[2]
Saccharomyces cerevisiae Sae2- and Tel1-dependent single-strand DNA formation at DNA break promotes microhomology-mediated end joining.

Genetics. 2007-8

[3]
MRX-dependent DNA damage response to short telomeres.

Mol Biol Cell. 2007-8

[4]
A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends.

Mol Cell. 2007-5-11

[5]
Independent sorting-out of thousands of duplicated gene pairs in two yeast species descended from a whole-genome duplication.

Proc Natl Acad Sci U S A. 2007-5-15

[6]
Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions.

Nat Struct Mol Biol. 2007-4

[7]
DNA breaks are masked by multiple Rap1 binding in yeast: implications for telomere capping and telomerase regulation.

Genes Dev. 2007-2-1

[8]
A topological mechanism for TRF2-enhanced strand invasion.

Nat Struct Mol Biol. 2007-2

[9]
Telomere structure and function in trypanosomes: a proposal.

Nat Rev Microbiol. 2007-1

[10]
Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination.

Nat Cell Biol. 2006-8

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