Premium
An essential DNA strand‐exchange activity is conserved in the divergent N‐termini of BLM orthologs
Author(s) -
Chen ChiFu,
Brill Steven J
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.61
Subject(s) - biology , bloom syndrome , genetics , dna , helicase , homologous recombination , saccharomyces cerevisiae , synthetic lethality , gene , conserved sequence , holliday junction , dna repair , dna damage , rna , peptide sequence
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.