Homology sensing via non-linear amplification of sequence dependent pausing by RecQ helicase

Yeonee Seol, Gábor M. Harami, Mihály Kovács, Keir C. Neuman

Research output: Contribution to journalArticle

Abstract

RecQ helicases promote genomic stability through their unique ability to suppress illegitimate recombination and resolve recombination intermediates. These DNA structure-specific activities of RecQ helicases are mediated by the helicase-and-RNAseD like C-terminal (HRDC) domain, via unknown mechanisms. Here, employing single-molecule magnetic tweezers and rapid kinetic approaches we establish that the HRDC domain stabilizes intrinsic, sequence-dependent, pauses of the core helicase (lacking the HRDC) in a DNA geometry-dependent manner. We elucidate the core unwinding mechanism in which the unwinding rate depends on the stability of the duplex DNA leading to transient sequence-dependent pauses. We further demonstrate a non-linear amplification of these transient pauses by the controlled binding of the HRDC domain. The resulting DNA sequence- and geometry-dependent pausing may underlie a homology sensing mechanism that allows rapid disruption of unstable (illegitimate) and stabilization of stable (legitimate) DNA strand invasions, which suggests an intrinsic mechanism of recombination quality control by RecQ helicases.

Original languageEnglish
Article numbere45909
JournaleLife
Volume8
DOIs
Publication statusPublished - Aug 2019

Keywords

  • DNA helicase
  • Genome stability
  • Homologous recombination
  • Magnetic tweezers
  • Single molecule biophysics
  • Unwinding mechanism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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