Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans

Marek Sebesta, Peter Burkovics, Szilvia Juhasz, Sufang Zhang, Judit E. Szabo, Marietta Y W T Lee, L. Haracska, Lumir Krejci

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Homologous recombination (HR) is essential for maintaining genomic integrity, which is challenged by a wide variety of potentially lethal DNA lesions. Regardless of the damage type, recombination is known to proceed by RAD51-mediated D-loop formation, followed by DNA repair synthesis. Nevertheless, the participating polymerases and extension mechanism are not well characterized. Here, we present a reconstitution of this step using purified human proteins. In addition to Pol δ, TLS polymerases, including Pol η and Pol κ, also can extend D-loops. In vivo characterization reveals that Pol η and Pol κ are involved in redundant pathways for HR. In addition, the presence of PCNA on the D-loop regulates the length of the extension tracks by recruiting various polymerases and might present a regulatory point for the various recombination outcomes.

Original languageEnglish
Pages (from-to)691-698
Number of pages8
JournalDNA Repair
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Homologous Recombination
Proliferating Cell Nuclear Antigen
Genetic Recombination
DNA
DNA Repair
Repair
Proteins

Keywords

  • D-loop
  • DNA repair synthesis
  • Homologous recombination
  • Reconstitution
  • TLS polymerases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sebesta, M., Burkovics, P., Juhasz, S., Zhang, S., Szabo, J. E., Lee, M. Y. W. T., ... Krejci, L. (2013). Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans. DNA Repair, 12(9), 691-698. https://doi.org/10.1016/j.dnarep.2013.05.001

Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans. / Sebesta, Marek; Burkovics, Peter; Juhasz, Szilvia; Zhang, Sufang; Szabo, Judit E.; Lee, Marietta Y W T; Haracska, L.; Krejci, Lumir.

In: DNA Repair, Vol. 12, No. 9, 09.2013, p. 691-698.

Research output: Contribution to journalArticle

Sebesta, M, Burkovics, P, Juhasz, S, Zhang, S, Szabo, JE, Lee, MYWT, Haracska, L & Krejci, L 2013, 'Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans', DNA Repair, vol. 12, no. 9, pp. 691-698. https://doi.org/10.1016/j.dnarep.2013.05.001
Sebesta, Marek ; Burkovics, Peter ; Juhasz, Szilvia ; Zhang, Sufang ; Szabo, Judit E. ; Lee, Marietta Y W T ; Haracska, L. ; Krejci, Lumir. / Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans. In: DNA Repair. 2013 ; Vol. 12, No. 9. pp. 691-698.
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