Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability.

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Version: Final published version
Serval ID
serval:BIB_969703C2985D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability.
Journal
Genes and Development
Author(s)
Su X.A., Dion V., Gasser S.M., Freudenreich C.H.
ISSN
1549-5477 (Electronic)
ISSN-L
0890-9369
Publication state
Published
Issued date
2015
Volume
29
Number
10
Pages
1006-1017
Language
english
Abstract
Secondary structure-forming DNA sequences such as CAG repeats interfere with replication and repair, provoking fork stalling, chromosome fragility, and recombination. In budding yeast, we found that expanded CAG repeats are more likely than unexpanded repeats to localize to the nuclear periphery. This positioning is transient, occurs in late S phase, requires replication, and is associated with decreased subnuclear mobility of the locus. In contrast to persistent double-stranded breaks, expanded CAG repeats at the nuclear envelope associate with pores but not with the inner nuclear membrane protein Mps3. Relocation requires Nup84 and the Slx5/8 SUMO-dependent ubiquitin ligase but not Rad51, Mec1, or Tel1. Importantly, the presence of the Nup84 pore subcomplex and Slx5/8 suppresses CAG repeat fragility and instability. Repeat instability in nup84, slx5, or slx8 mutant cells arises through aberrant homologous recombination and is distinct from instability arising from the loss of ligase 4-dependent end-joining. Genetic and physical analysis of Rad52 sumoylation and binding at the CAG tract suggests that Slx5/8 targets sumoylated Rad52 for degradation at the pore to facilitate recovery from acute replication stress by promoting replication fork restart. We thereby confirmed that the relocation of damage to nuclear pores plays an important role in a naturally occurring repair process.
Keywords
CAG repeats, chromosome fragility, repeat expansion, nuclear pore, Slx5/Slx8, nuclear organization
Pubmed
Web of science
Open Access
Yes
Create date
29/06/2015 10:10
Last modification date
20/08/2019 14:58
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