Format

Send to

Choose Destination
Genes Dev. 2016 Jun 1;30(11):1339-56. doi: 10.1101/gad.278275.116.

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

Author information

1
Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College, London W12 0NN, United Kingdom; Deptartment of Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida, Universitat de Lleida, 25198 Lleida, Spain;
2
Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca, 37007 Salamanca, Spain.
3
Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College, London W12 0NN, United Kingdom;
4
Deptartment of Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida, Universitat de Lleida, 25198 Lleida, Spain;

Abstract

The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, from end resection to Holliday junction (HJ) dissolution. Sgs1 has both pro- and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment and activation of Sgs1 at damaged sites are unknown. Here we show a two-step role for Smc5/6 in recruiting and activating Sgs1 through SUMOylation. First, auto-SUMOylation of Smc5/6 subunits leads to recruitment of Sgs1 as part of the STR (Sgs1-Top3-Rmi1) complex, mediated by two SUMO-interacting motifs (SIMs) on Sgs1 that specifically recognize SUMOylated Smc5/6. Second, Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for the efficient function of STR. Sgs1 mutants impaired in recognition of SUMOylated Smc5/6 (sgs1-SIMΔ) or SUMO-dead alleles (sgs1-KR) exhibit unprocessed HJs at damaged replication forks, increased crossover frequencies during double-strand break repair, and severe impairment in DNA end resection. Smc5/6 is a key regulator of Sgs1's recombination functions.

KEYWORDS:

Sgs1–Top3; Smc complexes; Smc5/6; genome stability; homologous recombination

PMID:
27298337
PMCID:
PMC4911932
DOI:
10.1101/gad.278275.116
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center