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The HRDC domain of BLM is required for the dissolution of double Holliday junctions
Author(s) -
Wu Leonard,
Lung Chan Kok,
Ralf Christine,
Bernstein Douglas A,
Garcia Patrick L,
Bohr Vilhelm A,
Vindigni Alessandro,
Janscak Pavel,
Keck James L,
Hickson Ian D
Publication year - 2005
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/sj.emboj.7600740
Subject(s) - holliday junction , biology , domain (mathematical analysis) , biophysics , genetics , homologous recombination , dna , mathematical analysis , mathematics
Bloom's syndrome is a hereditary cancer‐predisposition disorder resulting from mutations in the BLM gene. In humans, BLM encodes one of five members of the RecQ helicase family. One function of BLM is to act in concert with topoisomerase IIIα (TOPO IIIα) to resolve recombination intermediates containing double Holliday junctions by a process called double Holliday junction dissolution, herein termed dissolution. Here, we show that dissolution is highly specific for BLM among human RecQ helicases and critically depends upon a functional HRDC domain in BLM. We show that the HRDC domain confers DNA structure specificity, and is required for the efficient binding to and unwinding of double Holliday junctions, but not for the unwinding of a simple partial duplex substrate. Furthermore, we show that lysine‐1270 of BLM, which resides in the HRDC domain and is predicted to play a role in mediating interactions with DNA, is required for efficient dissolution.