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

First Author  Chen CF Year  2010
Journal  EMBO J Volume  29
Issue  10 Pages  1713-25
PubMed ID  20389284 Mgi Jnum  J:159365
Mgi Id  MGI:4442512 Doi  10.1038/emboj.2010.61
Citation  Chen CF, et al. (2010) An essential DNA strand-exchange activity is conserved in the divergent N-termini of BLM orthologs. EMBO J 29(10):1713-25
abstractText  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 top3Delta 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.
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