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Ubiquitination and deubiquitination of PCNA in response to stalling of the replication fork
journal contribution
posted on 2023-06-08, 07:59 authored by Stephanie Brown, Atsuko Niimi, Alan LehmannAlan LehmannFollowing exposure of human cells to DNA damaging agents that block the progress of the replication fork, mono-ubiquitination of PCNA mediates the switch from replicative DNA polymerases to polymerases specialised for translesion synthesis. We have shown that this modification of PCNA is necessary for the survival of cells after UV-irradiation and methyl methanesulfonate, that it is independent of cell cycle checkpoint activation, and that it persists after UV damage has been removed. In this Extra-view, we compare the regulation and biological significance of PCNA ubiquitination following treatments with UV light and the replication inhibitor hydroxyurea. We show that ubiquitination persists after removal of the replication block in both cases. With UV however, the persistence of ubiquitinated PCNA correlates with disappearance of the PCNA deubiquitinating enzyme USP1, whereas this is not the case for HU. Prevention of PCNA ubiquitination sensitises the cells to killing by both UV and HU.
History
Publication status
- Published
File Version
- Accepted version
Journal
Cell CycleISSN
1538-4101Publisher
Landes BioscienceExternal DOI
Issue
5Volume
8Page range
689-692Pages
4.0Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes