PCNA Unloading Is Crucial for the Bypass of DNA Lesions Using Homologous Recombination

Matan Arbel-Groissman, Batia Liefshitz, Nir Katz, Maxim Kuryachiy, Martin Kupiec*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

DNA Damage Tolerance (DDT) mechanisms allow cells to bypass lesions in the DNA during replication. This allows the cells to progress normally through the cell cycle in the face of abnormalities in their DNA. PCNA, a homotrimeric sliding clamp complex, plays a central role in the coordination of various processes during DNA replication, including the choice of mechanism used during DNA damage bypass. Mono-or poly-ubiquitination of PCNA facilitates an error-prone or an error-free bypass mechanism, respectively. In contrast, SUMOylation recruits the Srs2 helicase, which prevents local homologous recombination. The Elg1 RFC-like complex plays an important role in unloading PCNA from the chromatin. We analyze the interaction of mutations that destabilize PCNA with mutations in the Elg1 clamp unloader and the Srs2 helicase. Our results suggest that, in addition to its role as a coordinator of bypass mechanisms, the very presence of PCNA on the chromatin prevents homologous recombination, even in the absence of the Srs2 helicase. Thus, PCNA unloading seems to be a pre-requisite for recombinational repair.

Original languageEnglish
Article number3359
JournalInternational Journal of Molecular Sciences
Volume25
Issue number6
DOIs
StatePublished - Mar 2024

Funding

FundersFunder number
Israel Science Foundation
Minerva Foundation
German DFG
Milner Foundation

    Keywords

    • DNA damage bypass
    • DNA repair
    • DNA replication
    • Elg1
    • PCNA
    • SUMO
    • Saccharomyces cerevisiae
    • Srs2
    • post-replicational repair
    • ubiquitin

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