Cooperation of replication protein A with the ubiquitin ligase Rad18 in DNA damage bypass.
Replicative DNA damage bypass promotes cell viability in the presence of genotoxic agents but at the same time may lead to mutations, thereby contributing to genomic instability. In eukaryotes, DNA damage bypass is mediated by damage-induced ubiquitylation of the sliding clamp protein, proliferating cell nuclear antigen (PCNA). We have recently shown that replication protein A (RPA), a single-stranded (ss)DNA-binding protein essential for DNA replication, repair and recombination, is required for PCNA ubiquitylation in budding yeast. Both in yeast and in mammalian cells, RPA physically interacts with Rad18, the ubiquitin ligase responsible for PCNA mono-ubiquitylation. The association of Rad18 with chromatin correlates with that of RPA, and purified RPA can recruit the ligase to ssDNA in vitro. Here we have examined in more detail the interactions between Rad18, RPA and DNA and discuss their contribution to the activation of DNA damage bypass.
Huttner
Diana
D
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK.
Ulrich
Helle D
HD
D004249:DNA Damage; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008954:Models, Biological; D009994:Osmolar Concentration; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011485:Protein Binding; D051716:Replication Protein A / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; C063607:RAD18 protein, S cerevisiae; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases