puc-header

Non-Recombinogenic Role for Rad52, Rad51 and Rad57 in Translesion Synthesis

43 Pages Posted: 7 May 2019 Sneak Peek Status: Review Complete

See all articles by María I. Cano-Linares

María I. Cano-Linares

University Pablo Olavide of Seville - Department of Genome Biology

Néstor García-Rodriguez

Institute of Molecular Biology (IMB)

Aurora Yañez-Vilches

University Pablo Olavide of Seville - Department of Genome Biology

Román González-Prieto

University Pablo Olavide of Seville - Department of Genome Biology

Pedro San-Segundo

University of Salamanca - Institute of Functional Biology and Genomics (IBFG)

Helle D. Ulrich

Institute of Molecular Biology (IMB)

Felix Prado

University Pablo Olavide of Seville - Department of Genome Biology

More...

Abstract

DNA damage tolerance relies on homologous recombination (HR) and translesion synthesis (TLS) mechanisms to fill in the ssDNA gaps generated during the replication fork bypass of blocking DNA lesions. Whereas TLS requires specialized polymerases able to incorporate a dNTP opposite the lesion and is error-prone, HR uses the sister chromatid to repair the ssDNA gap and is mostly error-free. We report that the HR proteins Rad52, Rad51 and Rad57 act in concert with the TLS machinery (Rad6/Rad18-mediated PCNA ubiquitylation and polymerases Rev1/Pol ζ) to repair ssDNA gaps through a non-recombinogenic function, and accordingly they are required for DNA damage-induced mutagenesis. Specifically, Rad52, Rad51 and Rad57, but not Rad54, facilitate Rad6/Rad18 binding to chromatin and subsequent DNA damage-induced PCNA ubiquitylation. In sum, Rad51, Rad52 and Rad57 drive the tolerance process to HR or TLS through recombinational and non-recombinational functions, providing a novel role for the recombination proteins in maintaining genome integrity.

Keywords: DNA damage tolerance, homologous recombination, template switching, translesion synthesis, Rad52, Rad51, Rad18, mutagénesis, Rev1, Pol ζ

Suggested Citation

Cano-Linares, María I. and García-Rodriguez, Néstor and Yañez-Vilches, Aurora and González-Prieto, Román and San-Segundo, Pedro and Ulrich, Helle D. and Prado, Felix, Non-Recombinogenic Role for Rad52, Rad51 and Rad57 in Translesion Synthesis (May 7, 2019). Available at SSRN: https://ssrn.com/abstract=3383794 or http://dx.doi.org/10.2139/ssrn.3383794
This is a paper under consideration at Cell Press and has not been peer-reviewed.

María I. Cano-Linares

University Pablo Olavide of Seville - Department of Genome Biology

Spain

Néstor García-Rodriguez

Institute of Molecular Biology (IMB)

Ackermannweg 4
55128 Mainz
Germany

Aurora Yañez-Vilches

University Pablo Olavide of Seville - Department of Genome Biology

Spain

Román González-Prieto

University Pablo Olavide of Seville - Department of Genome Biology

Spain

Pedro San-Segundo

University of Salamanca - Institute of Functional Biology and Genomics (IBFG)

Spain

Helle D. Ulrich

Institute of Molecular Biology (IMB)

Ackermannweg 4
55128 Mainz
Germany

Felix Prado (Contact Author)

University Pablo Olavide of Seville - Department of Genome Biology ( email )

Spain

Click here to go to Cell.com

Paper statistics

Abstract Views
589
Downloads
16