Opposing effects of the UV lesion repair protein XPA and UV bypass polymerase η on ATR checkpoint signaling

Autor: Muh-Ching Yee, Ryan D. Bomgarden, Karlene A. Cimprich, James M. Ford, Patrick J. Lupardus, Deena V. Soni
Rok vydání: 2006
Předmět:
DNA Repair
DNA repair
DNA damage
Ultraviolet Rays
Cell Cycle Proteins
Ataxia Telangiectasia Mutated Proteins
DNA-Directed DNA Polymerase
Biology
Protein Serine-Threonine Kinases
Xenopus Proteins
Article
General Biochemistry
Genetics and Molecular Biology
Cell Line
Mice
Xenopus laevis
Animals
Humans
Poly-ADP-Ribose Binding Proteins
Replication protein A
Molecular Biology
Adaptor Proteins
Signal Transducing
General Immunology and Microbiology
Chromatin binding
General Neuroscience
Cell Cycle
DNA Helicases
DNA
G2-M DNA damage checkpoint
Cell cycle
Phosphoproteins
Molecular biology
Xeroderma Pigmentosum Group A Protein
DNA-Binding Proteins
DNA Repair Enzymes
Exodeoxyribonucleases
Checkpoint Kinase 1
Oocytes
Phosphorylation
biological phenomena
cell phenomena
and immunity
Corrigendum
Protein Kinases
Nucleotide excision repair
DNA Damage
Signal Transduction
Zdroj: The EMBO Journal. 25:5036-5036
ISSN: 1460-2075
0261-4189
Popis: An essential component of the ATR (ataxia telangiectasia-mutated and Rad3-related)-activating structure is single-stranded DNA. It has been suggested that nucleotide excision repair (NER) can lead to activation of ATR by generating such a signal, and in yeast, DNA damage processing through the NER pathway is necessary for checkpoint activation during G1. We show here that ultraviolet (UV) radiation-induced ATR signaling is compromised in XPA-deficient human cells during S phase, as shown by defects in ATRIP (ATR-interacting protein) translocation to sites of UV damage, UV-induced phosphorylation of Chk1 and UV-induced replication protein A phosphorylation and chromatin binding. However, ATR signaling was not compromised in XPC-, CSB-, XPF- and XPG-deficient cells. These results indicate that damage processing is not necessary for ATR-mediated S-phase checkpoint activation and that the lesion recognition function of XPA may be sufficient. In contrast, XP-V cells deficient in the UV bypass polymerase eta exhibited enhanced ATR signaling. Taken together, these results suggest that lesion bypass and not lesion repair may raise the level of UV damage that can be tolerated before checkpoint activation, and that XPA plays a critical role in this activation.
Databáze: OpenAIRE
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