Processive translocation mechanism of the human Bloom's syndrome helicase along single-stranded DNA

Máté Gyimesi, Kata Sarlós, M. Kovács

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

BLM, one of the human RecQ helicases, plays a fun- damental role in homologous recombination-based error-free DNA repair pathways, which require its translocation and DNA unwinding activities. Although translocation is essential in vivo during DNA repair processes and it provides a framework for more complex activities of helicases, including strand separation and nucleoprotein displacement, its mechanism has not been resolved for any human DNA helicase. Here, we present a quantitative model for the translocation of a monomeric form of BLM along ssDNA. We show that BLM performs translocation at a low adenosine triphosphate (ATP) coupling ratio (1 ATP consumed/1 nucleotide traveled) and moderate processivity (with a mean number of 50 nucleotides traveled in a single run). We also show that the rate-limiting step of the translocation cycle is a transition between two ADP-bound enzyme states. Via opening of the helicase core, this structural change may drive the stepping of BLM along the DNA track by a directed inchworm mechanism. The data also support the conclusion that BLM performs double-stranded DNA unwinding by fully active duplex destabilization.

Original languageEnglish
Article numbergkq145
Pages (from-to)4404-4414
Number of pages11
JournalNucleic Acids Research
Volume38
Issue number13
DOIs
Publication statusPublished - Mar 8 2010

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Bloom Syndrome
Single-Stranded DNA
DNA Repair
DNA
Nucleotides
Adenosine Triphosphate
RecQ Helicases
DNA Helicases
Nucleoproteins
Homologous Recombination
Adenosine Diphosphate
Enzymes
Bloom syndrome protein

ASJC Scopus subject areas

  • Genetics

Cite this

Processive translocation mechanism of the human Bloom's syndrome helicase along single-stranded DNA. / Gyimesi, Máté; Sarlós, Kata; Kovács, M.

In: Nucleic Acids Research, Vol. 38, No. 13, gkq145, 08.03.2010, p. 4404-4414.

Research output: Contribution to journalArticle

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