Article
Non-recombinogenic roles for Rad52 in translesion synthesis during DNA damage tolerance
Author/s | Cano Linares, María Isabel
Yáñez Vilches, Aurora García Rodríguez, Néstor Barrientos Moreno, Marta González Prieto, Román San Segundo, Pedro Ulrich, Helle D. Prado, Félix |
Department | Universidad de Sevilla. Departamento de Genética |
Publication Date | 2021 |
Deposit Date | 2021-09-23 |
Published in |
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Abstract | DNA damage tolerance relies on homologous recombination (HR) and translesion synthesis (TLS) mechanisms to fill in the ssDNA gaps generated during passing of the replication fork over DNA lesions in the template. Whereas ... DNA damage tolerance relies on homologous recombination (HR) and translesion synthesis (TLS) mechanisms to fill in the ssDNA gaps generated during passing of the replication fork over DNA lesions in the template. Whereas TLS requires specialized polymerases able to incorporate a dNTP opposite the lesion and is error-prone, HR uses the sister chromatid and is mostly error-free. We report that the HR protein Rad52—but not Rad51 and Rad57—acts in concert with the TLS machinery (Rad6/Rad18-mediated PCNA ubiquitylation and polymerases Rev1/Pol ζ) to repair MMS and UV light-induced ssDNA gaps through a non-recombinogenic mechanism, as inferred from the different phenotypes displayed in the absence of Rad52 and Rad54 (essential for MMS- and UV-induced HR); accordingly, Rad52 is required for efficient DNA damage-induced mutagenesis. In addition, Rad52, Rad51, and Rad57, but not Rad54, facilitate Rad6/Rad18 binding to chromatin and subsequent DNA damage-induced PCNA ubiquitylation. Therefore, Rad52 facilitates the tolerance process not only by HR but also by TLS through Rad51/Rad57-dependent and -independent processes, providing a novel role for the recombination proteins in maintaining genome integrity. |
Project ID. | BFU2015-63698-P
PGC2018-099182-B-I00 BFU2015-65417-R RTI2018-099055-B-I00 BFU2015-69142-REDT ERC-AdG323179 |
Citation | Cano Linares, M.I., Yáñez Vilches, A., García Rodríguez, N., Barrientos Moreno, M., González Prieto, R., San Segundo, P.,...,Prado, F. (2021). Non-recombinogenic roles for Rad52 in translesion synthesis during DNA damage tolerance. EMBO Reports, 22 (1), e50410. |
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