Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>

ABSTRACT During DNA replication, stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances, the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesion...

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Autores principales:	Matan Arbel, Alex Bronstein, Soumitra Sau, Batia Liefshitz, Martin Kupiec
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	DNA repair Elg1 Rad52 salvage pathway Srs2 homologous recombination Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c6fb9d83f3524b178fcfaa153a1f91ba
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spelling	oai:doaj.org-article:c6fb9d83f3524b178fcfaa153a1f91ba2021-11-15T15:56:46ZAccess to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>10.1128/mBio.00705-202150-7511https://doaj.org/article/c6fb9d83f3524b178fcfaa153a1f91ba2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00705-20https://doaj.org/toc/2150-7511ABSTRACT During DNA replication, stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances, the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesions encountered during DNA replication. PCNA can also be SUMOylated at the same residue or at lysine 127. Surprisingly, pol30-K164R mutants display a higher degree of sensitivity to DNA-damaging agents than pol30-KK127,164RR strains, unable to modify any of the lysines. Here, we show that in addition to translesion synthesis and strand-transfer DDT mechanisms, an alternative repair mechanism (“salvage recombination”) that copies information from the sister chromatid is repressed by the recruitment of Srs2 to SUMOylated PCNA. Overexpression of Elg1, the PCNA unloader, or of the recombination protein Rad52 allows its activation. We dissect the genetic requirements for this pathway, as well as the interactions between Srs2 and Elg1. IMPORTANCE PCNA, the ring that encircles DNA maintaining the processivity of DNA polymerases, is modified by ubiquitin and SUMO. Whereas ubiquitin is required for bypassing lesions through the DNA damage tolerance (DDT) pathways, we show here that SUMOylation represses another pathway, salvage recombination. The Srs2 helicase is recruited to SUMOylated PCNA and prevents the salvage pathway from acting. The pathway can be induced by overexpressing the PCNA unloader Elg1, or the homologous recombination protein Rad52. Our results underscore the role of PCNA modifications in controlling the various bypass and DNA repair mechanisms.Matan ArbelAlex BronsteinSoumitra SauBatia LiefshitzMartin KupiecAmerican Society for MicrobiologyarticleDNA repairElg1Rad52salvage pathwaySrs2homologous recombinationMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA repair Elg1 Rad52 salvage pathway Srs2 homologous recombination Microbiology QR1-502
spellingShingle	DNA repair Elg1 Rad52 salvage pathway Srs2 homologous recombination Microbiology QR1-502 Matan Arbel Alex Bronstein Soumitra Sau Batia Liefshitz Martin Kupiec Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
description	ABSTRACT During DNA replication, stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances, the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesions encountered during DNA replication. PCNA can also be SUMOylated at the same residue or at lysine 127. Surprisingly, pol30-K164R mutants display a higher degree of sensitivity to DNA-damaging agents than pol30-KK127,164RR strains, unable to modify any of the lysines. Here, we show that in addition to translesion synthesis and strand-transfer DDT mechanisms, an alternative repair mechanism (“salvage recombination”) that copies information from the sister chromatid is repressed by the recruitment of Srs2 to SUMOylated PCNA. Overexpression of Elg1, the PCNA unloader, or of the recombination protein Rad52 allows its activation. We dissect the genetic requirements for this pathway, as well as the interactions between Srs2 and Elg1. IMPORTANCE PCNA, the ring that encircles DNA maintaining the processivity of DNA polymerases, is modified by ubiquitin and SUMO. Whereas ubiquitin is required for bypassing lesions through the DNA damage tolerance (DDT) pathways, we show here that SUMOylation represses another pathway, salvage recombination. The Srs2 helicase is recruited to SUMOylated PCNA and prevents the salvage pathway from acting. The pathway can be induced by overexpressing the PCNA unloader Elg1, or the homologous recombination protein Rad52. Our results underscore the role of PCNA modifications in controlling the various bypass and DNA repair mechanisms.
format	article
author	Matan Arbel Alex Bronstein Soumitra Sau Batia Liefshitz Martin Kupiec
author_facet	Matan Arbel Alex Bronstein Soumitra Sau Batia Liefshitz Martin Kupiec
author_sort	Matan Arbel
title	Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_short	Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_full	Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_fullStr	Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_full_unstemmed	Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_sort	access to pcna by srs2 and elg1 controls the choice between alternative repair pathways in <named-content content-type="genus-species">saccharomyces cerevisiae</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/c6fb9d83f3524b178fcfaa153a1f91ba
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Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>

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