An essential DNA strand-exchange activity is conserved in the divergent N-termini of BLM orthologs

The gene mutated in Bloom's syndrome, BLM , encodes a member of the RecQ family of DNA helicases that is needed to suppress genome instability and cancer predisposition. BLM is highly conserved and all BLM orthologs, including budding yeast Sgs1, have a large N‐terminus that binds Top3–Rmi1 but...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2010-05, Vol.29 (10), p.1713-1725
Main Authors: Chen, Chi-Fu, Brill, Steven J
Format: Article
Language:English
Subjects:
Alleles
Animals
BLM
Bloom Syndrome - genetics
Bloom's syndrome
Catalysis
Conserved Sequence
Deoxyribonucleic acid
DNA
DNA - genetics
DNA helicase
DNA Helicases - genetics
DNA, Single-Stranded - genetics
Drosophila
Drosophila melanogaster
EMBO13
Genomics
Humans
Kinetics
Molecular biology
Mutation
Protein Structure, Tertiary
RecQ Helicases - genetics
RecQ Helicases - physiology
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - physiology
Sgs1
synthetic lethality
Yeasts
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The gene mutated in Bloom's syndrome, BLM , encodes a member of the RecQ family of DNA helicases that is needed to suppress genome instability and cancer predisposition. BLM is highly conserved and all BLM orthologs, including budding yeast Sgs1, have a large N‐terminus that binds Top3–Rmi1 but has no known catalytic activity. In this study, we describe a sub‐domain of the Sgs1 N‐terminus that shows in vitro single‐strand DNA (ssDNA) binding, ssDNA annealing and strand‐exchange (SE) activities. These activities are conserved in the human and Drosophila orthologs. SE between duplex DNA and homologous ssDNA requires no cofactors and is inhibited by a single mismatched base pair. The SE domain of Sgs1 is required in vivo for the suppression of hyper‐recombination, suppression of synthetic lethality and heteroduplex rejection. The top3 Δ slow‐growth phenotype is also SE dependent. Surprisingly, the highly divergent human SE domain functions in yeast. This work identifies SE as a new molecular function of BLM/Sgs1, and we propose that at least one role of SE is to mediate the strand‐passage events catalysed by Top3–Rmi1.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2010.61