ATR-mediated phosphorylation of DNA polymerase η is needed for efficient recovery from UV damage.
DNA polymerase η (polη) belongs to the Y-family of DNA polymerases and facilitates translesion synthesis past UV damage. We show that, after UV irradiation, polη becomes phosphorylated at Ser601 by the ataxia-telangiectasia mutated and Rad3-related (ATR) kinase. DNA damage-induced phosphorylation of polη depends on its physical interaction with Rad18 but is independent of PCNA monoubiquitination. It requires the ubiquitin-binding domain of polη but not its PCNA-interacting motif. ATR-dependent phosphorylation of polη is necessary to restore normal survival and postreplication repair after ultraviolet irradiation in xeroderma pigmentosum variant fibroblasts, and is involved in the checkpoint response to UV damage. Taken together, our results provide evidence for a link between DNA damage-induced checkpoint activation and translesion synthesis in mammalian cells.
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, England, UK.
Thomas
T
Göhler
Simone
S
Sabbioneda
Catherine M
CM
Green
Alan R
AR
Lehmann
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004259:DNA-Directed DNA Polymerase; D017346:Protein Serine-Threonine Kinases; C576597:ATR protein, human; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases
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