2kv2 | pdb_00002kv2
Solution Structure of the human BLM HRDC domain
Structural highlights
Disease[BLM_HUMAN] Bloom syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function[BLM_HUMAN] Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE).[1] [2] [3] [4] Publication Abstract from PubMedThe helicase and RNaseD C-terminal (HRDC) domain, conserved among members of the RecQ helicase family, regulates helicase activity by virtue of variations in its surface residues. The HRDC domain of Bloom syndrome protein (BLM) is known as a critical determinant of the dissolution function of double Holliday junctions by the BLM-Topoisomerase IIIalpha complex. In this study, we determined the solution structure of the human BLM HRDC domain and characterized its DNA-binding activity. The BLM HRDC domain consists of five alpha-helices with a hydrophobic 3(10)-helical loop between helices 1 and 2 and an extended acidic surface comprising residues in helices 3-5. The BLM HRDC domain preferentially binds to ssDNA, though with a markedly low binding affinity (K(d) approximately 100 muM). NMR chemical shift perturbation studies suggested that the critical DNA-binding residues of the BLM HRDC domain are located in the hydrophobic loop and the N-terminus of helix 2. Interestingly, the isolated BLM HRDC domain had quite different DNA-binding modes between ssDNA and Holliday junctions in electrophoretic mobility shift assay experiments. Based on its surface charge separation and DNA-binding properties, we suggest that the HRDC domain of BLM may be adapted for a unique function among RecQ helicases-that of bridging protein and DNA interactions. Structure and function of the regulatory HRDC domain from human Bloom syndrome protein.,Kim YM, Choi BS Nucleic Acids Res. 2010 Nov 1;38(21):7764-77. Epub 2010 Jul 17. PMID:20639533[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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