A role for chromatin remodellers in replication of damaged DNA
Open Access
- 24 May 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 40 (15), 7393-7403
- https://doi.org/10.1093/nar/gks453
Abstract
In eukaryotic cells, replication past damaged sites in DNA is regulated by the ubiquitination of proliferating cell nuclear antigen (PCNA). Little is known about how this process is affected by chromatin structure. There are two isoforms of the Remodels the Structure of Chromatin (RSC) remodelling complex in yeast. We show that deletion of RSC2 results in a dramatic reduction in the level of PCNA ubiquitination after DNA-damaging treatments, whereas no such effect was observed after deletion of RSC1. Similarly, depletion of the BAF180 component of the corresponding PBAF (Polybromo BRG1 (Brahma-Related Gene 1) Associated Factor) complex in human cells led to a similar reduction in PCNA ubiquitination. Remarkably, we found that depletion of BAF180 resulted after UV-irradiation, in a reduction not only of ubiquitinated PCNA but also of chromatin-associated unmodified PCNA and Rad18 (the E3 ligase that ubiquitinates PCNA). This was accompanied by a modest decrease in fork progression. We propose a model to account for these findings that postulates an involvement of PBAF in repriming of replication downstream from replication forks blocked at sites of DNA damage. In support of this model, chromatin immunoprecipitation data show that the RSC complex in yeast is present in the vicinity of the replication forks, and by extrapolation, this is also likely to be the case for the PBAF complex in human cells.Keywords
This publication has 57 references indexed in Scilit:
- Human SNF5/INI1, a Component of the Human SWI/SNF Chromatin Remodeling Complex, Promotes Nucleotide Excision Repair by Influencing ATM Recruitment and Downstream H2AX PhosphorylationMolecular and Cellular Biology, 2009
- Involvement of a chromatin remodeling complex in damage tolerance during DNA replicationNature Structural & Molecular Biology, 2009
- Chromatin remodelling beyond transcription: the INO80 and SWR1 complexesNature Reviews Molecular Cell Biology, 2009
- Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cellsProceedings of the National Academy of Sciences of the United States of America, 2008
- PCNA Ubiquitination and REV1 Define Temporally Distinct Mechanisms for Controlling Translesion Synthesis in the Avian Cell Line DT40Molecular Cell, 2008
- Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damageCell Cycle, 2008
- ATP-dependent chromatin remodeling shapes the DNA replication landscapeNature Structural & Molecular Biology, 2008
- Ino80 Chromatin Remodeling Complex Promotes Recovery of Stalled Replication ForksCurrent Biology, 2008
- The Ino80 chromatin-remodeling enzyme regulates replisome function and stabilityNature Structural & Molecular Biology, 2008
- Activation of Ubiquitin-Dependent DNA Damage Bypass Is Mediated by Replication Protein AMolecular Cell, 2008