Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes

TY - JOUR

T1 - Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes

AU - Newman, Joseph A

AU - Savitsky, Pavel

AU - Allerston, Charles K

AU - Bizard, Anna H

AU - Özer, Özgün

AU - Sarlós, Kata

AU - Liu, Ying

AU - Pardon, Els

AU - Steyaert, Jan

AU - Hickson, Ian D

AU - Gileadi, Opher

N1 - © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2015/4/3

Y1 - 2015/4/3

N2 - Bloom's syndrome helicase (BLM) is a member of the RecQ family of DNA helicases, which play key roles in the maintenance of genome integrity in all organism groups. We describe crystal structures of the BLM helicase domain in complex with DNA and with an antibody fragment, as well as SAXS and domain association studies in solution. We show an unexpected nucleotide-dependent interaction of the core helicase domain with the conserved, poorly characterized HRDC domain. The BLM-DNA complex shows an unusual base-flipping mechanism with unique positioning of the DNA duplex relative to the helicase core domains. Comparison with other crystal structures of RecQ helicases permits the definition of structural transitions underlying ATP-driven helicase action, and the identification of a nucleotide-regulated tunnel that may play a role in interactions with complex DNA substrates.

AB - Bloom's syndrome helicase (BLM) is a member of the RecQ family of DNA helicases, which play key roles in the maintenance of genome integrity in all organism groups. We describe crystal structures of the BLM helicase domain in complex with DNA and with an antibody fragment, as well as SAXS and domain association studies in solution. We show an unexpected nucleotide-dependent interaction of the core helicase domain with the conserved, poorly characterized HRDC domain. The BLM-DNA complex shows an unusual base-flipping mechanism with unique positioning of the DNA duplex relative to the helicase core domains. Comparison with other crystal structures of RecQ helicases permits the definition of structural transitions underlying ATP-driven helicase action, and the identification of a nucleotide-regulated tunnel that may play a role in interactions with complex DNA substrates.

U2 - 10.1093/nar/gkv373

DO - 10.1093/nar/gkv373

M3 - Journal article

C2 - 25901030

SN - 0305-1048

VL - 43

SP - 5221

EP - 5235

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 10

ER -