Titre

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

Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Su, X.A.
Auteure/Auteur
Dion, V.
Auteure/Auteur
Gasser, S.M.
Auteure/Auteur
Freudenreich, C.H.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1549-5477
Statut éditorial
Publié
Date de publication
2015
Volume
29
Numéro
10
Première page
1006
Dernière page/numéro d’article
1017
Langue
anglais
Résumé
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.
Sujets

CAG repeats

chromosome fragility

repeat expansion

nuclear pore

Slx5/Slx8

nuclear organization

PID Serval
serval:BIB_969703C2985D
DOI
PMID
WOS
Permalien
Open Access
Oui
Date de création
2015-06-29T09:10:16.750Z
Date de création dans IRIS
2025-05-21T03:47:35Z
Fichier(s)
En cours de chargement...
Vignette d'image
Nom

1006.pdf

Version du manuscrit

published

Taille

518.88 KB

Format

Adobe PDF

PID Serval

serval:BIB_969703C2985D.P001

URN

urn:nbn:ch:serval-BIB_969703C2985D5

Somme de contrôle

(MD5):d8498291748f45c765105deec49e9d4d