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The structure of the RMI core complex resembles the RPA interface
Author(s) -
Hoadley Kelly A.,
Xu Dongyi,
Xue Yutong,
Wang Weidong,
Keck James L.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb44
Subject(s) - holliday junction , bloom syndrome , helicase , recq helicase , biology , dna , sister chromatid exchange , dna replication , genetics , genome instability , gene , homologous recombination , dna damage , rna
RecQ DNA helicases are ubiquitously conserved enzymes with critical roles in genome maintenance. BLM, the protein product of the gene mutated in Bloom's syndrome, is one of five human RecQ helicases. BLM functions as part of the “dissolvasome” complex, which includes TopoIIIα (a type IA topoisomerase), and the RMI (for RecQ‐Mediated Instability) subcomplex (RMI1 and RMI2). The dissolvasome separates double Holliday junction DNA without exchange of genetic material. Here we describe the 1.55 Å resolution structure of the RMI core complex, which includes RMI2 and the C‐terminal OB‐fold of RMI1. The overall structure strongly resembles two‐thirds of the trimerization interface of Replication Protein A (RPA). We examined the RMI interface using co‐immunoprecipitations with RMI2 variants and confirmed two key structural interactions. We probed the effects of complex‐destabilizing mutations on sister chromatid exchange (SCE) formation in chicken DT40 cells and discovered that mutations that disrupt the RMI interface cause an increase in SCE formation. We conclude that the RMI interface is crucial to the stability of the BLM dissolvasome. This research was funded by NIH R01‐GM068061.