Lysine Residue 185 of Rad1 Is a Topological but Not a Functional Counterpart of Lysine Residue 164 of PCNA

Monoubiquitylation of the homotrimeric DNA sliding clamp PCNA at lysine residue 164 (PCNA(K164)) is a highly conserved, DNA damage-inducible process that is mediated by the E2/E3 complex Rad6/Rad18. This ubiquitylation event recruits translesion synthesis (TLS) polymerases capable of replicating acr...

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Vydané v:	PloS one Ročník 6; číslo 1; s. e16669
Hlavní autori:	Wit, Niek, Krijger, Peter H. L., van den Berk, Paul C. M., Jacobs, Heinz
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 31.01.2011 Public Library of Science (PLoS)
Predmet:	Animals B cells Baking yeast Biology Cancer Cell cycle Cell growth Chemical synthesis CHK1 protein Class switching Crystal structure Cytokines Deoxyribonucleic acid DNA DNA Damage DNA polymerases Exonucleases - physiology Genes Hus1 protein Immunoglobulins Immunology Lysine Lysine - physiology Mammals Mice Models, Animal Mutation Proliferating cell nuclear antigen Proliferating Cell Nuclear Antigen - physiology Protein Processing, Post-Translational Rad1 protein Rad9 protein Recombination Replication Residues Saccharomyces cerevisiae Senescence Sliding Somatic hypermutation Ubiquitin Yeast Netherlands
ISSN:	1932-6203, 1932-6203
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Popis
Shrnutí:	Monoubiquitylation of the homotrimeric DNA sliding clamp PCNA at lysine residue 164 (PCNA(K164)) is a highly conserved, DNA damage-inducible process that is mediated by the E2/E3 complex Rad6/Rad18. This ubiquitylation event recruits translesion synthesis (TLS) polymerases capable of replicating across damaged DNA templates. Besides PCNA, the Rad6/Rad18 complex was recently shown in yeast to ubiquitylate also 9-1-1, a heterotrimeric DNA sliding clamp composed of Rad9, Rad1, and Hus1 in a DNA damage-inducible manner. Based on the highly similar crystal structures of PCNA and 9-1-1, K185 of Rad1 (Rad1(K185)) was identified as the only topological equivalent of PCNA(K164). To investigate a potential role of posttranslational modifications of Rad1(K185) in DNA damage management, we here generated a mouse model with a conditional deletable Rad1(K185R) allele. The Rad1(K185) residue was found to be dispensable for Chk1 activation, DNA damage survival, and class switch recombination of immunoglobulin genes as well as recruitment of TLS polymerases during somatic hypermutation of immunoglobulin genes. Our data indicate that Rad1(K185) is not a functional counterpart of PCNA(K164).
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: NW HJ. Performed the experiments: NW PHLK PCMvdB. Analyzed the data: NW HJ. Wrote the manuscript: NW HJ.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0016669