Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains

Máté Gyimesi, Gábor M. Harami, Kata Sarlós, Eszter Hazai, Zsolt Bikádi, M. Kovács

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Bloom's syndrome DNA helicase (BLM), a member of the RecQ family, is a key player in homologous recombination (HR)-based error-free DNA repair processes. During HR, BLM exerts various biochemical activities including single-stranded (ss) DNA translocation, separation and annealing of complementary DNA strands, disruption of complex DNA structures (e.g. displacement loops) and contributes to quality control of HR via clearance of Rad51 nucleoprotein filaments. We performed a quantitative mechanistic analysis of truncated BLM constructs that are shorter than the previously identified minimal functional module. Surprisingly, we found that a BLM construct comprising only the two conserved RecA domains and the Zn2+-binding domain (residues 642-1077) can efficiently perform all mentioned HR-related activities. The results demonstrate that the Zn2+-binding domain is necessary for functional interaction with DNA. We show that the extensions of this core, including the winged-helix domain and the strand separation hairpin identified therein in other RecQ-family helicases, are not required for mechanochemical activity per se and may instead play modulatory roles and mediate protein-protein interactions.

Original languageEnglish
Pages (from-to)3952-3963
Number of pages12
JournalNucleic Acids Research
Volume40
Issue number9
DOIs
Publication statusPublished - May 2012

Fingerprint

Bloom Syndrome
Homologous Recombination
Human Activities
RecQ Helicases
DNA Helicases
Nucleoproteins
Single-Stranded DNA
DNA
DNA Repair
Quality Control
Proteins
Complementary DNA
Bloom syndrome protein

ASJC Scopus subject areas

  • Genetics

Cite this

Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains. / Gyimesi, Máté; Harami, Gábor M.; Sarlós, Kata; Hazai, Eszter; Bikádi, Zsolt; Kovács, M.

In: Nucleic Acids Research, Vol. 40, No. 9, 05.2012, p. 3952-3963.

Research output: Contribution to journalArticle

Gyimesi, Máté ; Harami, Gábor M. ; Sarlós, Kata ; Hazai, Eszter ; Bikádi, Zsolt ; Kovács, M. / Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains. In: Nucleic Acids Research. 2012 ; Vol. 40, No. 9. pp. 3952-3963.
@article{492400b306a54826bea411ddb62db0db,
title = "Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains",
abstract = "Bloom's syndrome DNA helicase (BLM), a member of the RecQ family, is a key player in homologous recombination (HR)-based error-free DNA repair processes. During HR, BLM exerts various biochemical activities including single-stranded (ss) DNA translocation, separation and annealing of complementary DNA strands, disruption of complex DNA structures (e.g. displacement loops) and contributes to quality control of HR via clearance of Rad51 nucleoprotein filaments. We performed a quantitative mechanistic analysis of truncated BLM constructs that are shorter than the previously identified minimal functional module. Surprisingly, we found that a BLM construct comprising only the two conserved RecA domains and the Zn2+-binding domain (residues 642-1077) can efficiently perform all mentioned HR-related activities. The results demonstrate that the Zn2+-binding domain is necessary for functional interaction with DNA. We show that the extensions of this core, including the winged-helix domain and the strand separation hairpin identified therein in other RecQ-family helicases, are not required for mechanochemical activity per se and may instead play modulatory roles and mediate protein-protein interactions.",
author = "M{\'a}t{\'e} Gyimesi and Harami, {G{\'a}bor M.} and Kata Sarl{\'o}s and Eszter Hazai and Zsolt Bik{\'a}di and M. Kov{\'a}cs",
year = "2012",
month = "5",
doi = "10.1093/nar/gks008",
language = "English",
volume = "40",
pages = "3952--3963",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains

AU - Gyimesi, Máté

AU - Harami, Gábor M.

AU - Sarlós, Kata

AU - Hazai, Eszter

AU - Bikádi, Zsolt

AU - Kovács, M.

PY - 2012/5

Y1 - 2012/5

N2 - Bloom's syndrome DNA helicase (BLM), a member of the RecQ family, is a key player in homologous recombination (HR)-based error-free DNA repair processes. During HR, BLM exerts various biochemical activities including single-stranded (ss) DNA translocation, separation and annealing of complementary DNA strands, disruption of complex DNA structures (e.g. displacement loops) and contributes to quality control of HR via clearance of Rad51 nucleoprotein filaments. We performed a quantitative mechanistic analysis of truncated BLM constructs that are shorter than the previously identified minimal functional module. Surprisingly, we found that a BLM construct comprising only the two conserved RecA domains and the Zn2+-binding domain (residues 642-1077) can efficiently perform all mentioned HR-related activities. The results demonstrate that the Zn2+-binding domain is necessary for functional interaction with DNA. We show that the extensions of this core, including the winged-helix domain and the strand separation hairpin identified therein in other RecQ-family helicases, are not required for mechanochemical activity per se and may instead play modulatory roles and mediate protein-protein interactions.

AB - Bloom's syndrome DNA helicase (BLM), a member of the RecQ family, is a key player in homologous recombination (HR)-based error-free DNA repair processes. During HR, BLM exerts various biochemical activities including single-stranded (ss) DNA translocation, separation and annealing of complementary DNA strands, disruption of complex DNA structures (e.g. displacement loops) and contributes to quality control of HR via clearance of Rad51 nucleoprotein filaments. We performed a quantitative mechanistic analysis of truncated BLM constructs that are shorter than the previously identified minimal functional module. Surprisingly, we found that a BLM construct comprising only the two conserved RecA domains and the Zn2+-binding domain (residues 642-1077) can efficiently perform all mentioned HR-related activities. The results demonstrate that the Zn2+-binding domain is necessary for functional interaction with DNA. We show that the extensions of this core, including the winged-helix domain and the strand separation hairpin identified therein in other RecQ-family helicases, are not required for mechanochemical activity per se and may instead play modulatory roles and mediate protein-protein interactions.

UR - http://www.scopus.com/inward/record.url?scp=84861395477&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861395477&partnerID=8YFLogxK

U2 - 10.1093/nar/gks008

DO - 10.1093/nar/gks008

M3 - Article

C2 - 22253018

AN - SCOPUS:84861395477

VL - 40

SP - 3952

EP - 3963

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 9

ER -