Structure and function of the regulatory HRDC domain from human Bloom syndrome protein.

Nucleic Acids Research
Young Mee Kim, Byong-Seok Choi

Abstract

The 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 IIIα 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 α-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) ∼100 μM). 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 ...Continue Reading

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Feb 18, 2021·Cell Chemical Biology·Pauline LejaultDavid Monchaud

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Methods Mentioned

BETA
NMR
electrophoretic mobility shift
PCR
electrophoresis
protein assay
gel filtration

Software Mentioned

TALOS
SPARKY3
TINA
Sparky
PyMOL
NMRPipe
Kalign
MOLMOL
ExPASy ProtParam tool
DALI

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