Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination

Gábor M. Harami, Yeonee Seol, Junghoon In, Veronika Ferencziová, Máté Martina, Máté Gyimesi, Kata Sarlós, Zoltán J. Kovács, Nikolett T. Nagy, Yuze Sun, Tibor Vellai, Keir C. Neuman, M. Kovács

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cells must continuously repair inevitable DNA damage while avoiding the deleterious consequences of imprecise repair. Distinction between legitimate and illegitimate repair processes is thought to be achieved in part through differential recognition and processing of specific noncanonical DNA structures, although the mechanistic basis of discrimination remains poorly defined. Here, we show that Escherichia coli RecQ, a central DNA recombination and repair enzyme, exhibits differential processing of DNA substrates based on their geometry and structure. Through single-molecule and ensemble biophysical experiments, we elucidate how the conserved domain architecture of RecQ supports geometry-dependent shuttling and directed processing of recombination-intermediate [displacement loop (D-loop)] substrates. Our study shows that these activities together suppress illegitimate recombination in vivo, whereas unregulated duplex unwinding is detrimental for recombination precision. Based on these results, we propose a mechanism through which RecQ helicases achieve recombination precision and efficiency.

Original languageEnglish
Pages (from-to)E466-E475
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number4
DOIs
Publication statusPublished - Jan 24 2017

Fingerprint

RecQ Helicases
Homologous Recombination
Quality Control
Genetic Recombination
DNA
DNA Repair Enzymes
Recombinational DNA Repair
DNA Damage
Escherichia coli

Keywords

  • DNA unwinding
  • Helicase
  • Magnetic tweezers
  • RecQ
  • Single molecule

ASJC Scopus subject areas

  • General

Cite this

Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination. / Harami, Gábor M.; Seol, Yeonee; In, Junghoon; Ferencziová, Veronika; Martina, Máté; Gyimesi, Máté; Sarlós, Kata; Kovács, Zoltán J.; Nagy, Nikolett T.; Sun, Yuze; Vellai, Tibor; Neuman, Keir C.; Kovács, M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 4, 24.01.2017, p. E466-E475.

Research output: Contribution to journalArticle

Harami, GM, Seol, Y, In, J, Ferencziová, V, Martina, M, Gyimesi, M, Sarlós, K, Kovács, ZJ, Nagy, NT, Sun, Y, Vellai, T, Neuman, KC & Kovács, M 2017, 'Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 4, pp. E466-E475. https://doi.org/10.1073/pnas.1615439114
Harami, Gábor M. ; Seol, Yeonee ; In, Junghoon ; Ferencziová, Veronika ; Martina, Máté ; Gyimesi, Máté ; Sarlós, Kata ; Kovács, Zoltán J. ; Nagy, Nikolett T. ; Sun, Yuze ; Vellai, Tibor ; Neuman, Keir C. ; Kovács, M. / Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 4. pp. E466-E475.
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