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- Title
Ubiquitin/SUMO modification of PCNA promotes replication fork progression in Xenopus laevis egg extracts.
- Authors
Leach, Craig A.; Michael, W. Matthew
- Abstract
The homotrimeric DNA replication protein proliferating cell nuclear antigen (PCNA) is regulated by both ubiquilylation and sumoylation. We study the appearance and the impact of these modifications on chromosomal replication in frog egg extracts. Xenopus laevis PCNA is modified on lysine 164 by sumoylation, mono-ubiquitylation, and diubiquilylation. Sumoylation and monoubiquitylation occur during the replication of undamaged DNA, whereas diubiquitylation occurs specifically in response to DNA damage. When lysine 164 modification is prevented, replication fork movement through undamaged DNA slows down and DNA polymerase δ fails to associate with replicating chromatin. When sumoylation alone is prevented, replication occurs normally and neither monoubiquitylation nor sumoylation are required for the replication of simple single-strand DNA templates. Our findings expand the repertoire of functions for PCNA ubiquilylation and sumoylation by elucidating a role for these modifications during the replication of undamaged DNA. Furthermore, they suggest that PCNA monoubiquitylation serves as a molecular gas pedal that controls the speed of replisome movement during S phase.
- Subjects
DNA replication; CELL proliferation; ANTIGENS; PROTEINS; XENOPUS laevis
- Publication
Journal of Cell Biology, 2005, Vol 171, Issue 6, p947
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200508100