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Role of SUMO modification of human PCNA at stalled replication fork

Gali, Himabindu and Juhász, Szilvia and Mórocz, Mónika and Hajdú, Ildikó and Fátyol, Károly and Szukacsov, Valéria and Burkovics, Péter and Haracska, Lajos (2012) Role of SUMO modification of human PCNA at stalled replication fork. NUCLEIC ACIDS RESEARCH, 40 (13). pp. 6049-6059. ISSN 0305-1048

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Abstract

DNA double-strand breaks (DSBs) can be generated not only by reactive agents but also as a result of replication fork collapse at unrepaired DNA lesions. Whereas ubiquitylation of proliferating cell nuclear antigen (PCNA) facilitates damage bypass, modification of yeast PCNA by small ubiquitin-like modifier (SUMO) controls recombination by providing access for the Srs2 helicase to disrupt Rad51 nucleoprotein filaments. However, in human cells, the roles of PCNA SUMOylation have not been explored. Here, we characterize the modification of human PCNA by SUMO in vivo as well as in vitro. We establish that human PCNA can be SUMOylated at multiple sites including its highly conserved K164 residue and that SUMO modification is facilitated by replication factor C (RFC). We also show that expression of SUMOylation site PCNA mutants leads to increased DSB formation in the Rad18(-/-) cell line where the effect of Rad18-dependent K164 PCNA ubiquitylation can be ruled out. Moreover, expression of PCNA-SUMO1 fusion prevents DSB formation as well as inhibits recombination if replication stalls at DNA lesions. These findings suggest the importance of SUMO modification of human PCNA in preventing replication fork collapse to DSB and providing genome stability.

Item Type: Article
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 20 Sep 2021 14:33
Last Modified: 20 Sep 2021 14:33
URI: http://real.mtak.hu/id/eprint/129877

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