Chromatin association of rad17 is required for an ataxia telangiectasia and rad-related kinase-mediated S-phase checkpoint in response to low-dose ultraviolet radiation.
Activation of the S-phase checkpoint results in an inhibition of DNA synthesis in response to DNA damage. This is an active cellular response that may enhance cell survival and limit heritable genetic abnormalities. While much attention has been paid to elucidating signal transduction pathways regulating the ionizing radiation-induced S-phase checkpoint, less is known about whether UV radiation initiates the process and the mechanism controlling it. Here, we demonstrate that low-dose UV radiation activates an S-phase checkpoint that requires the ataxia telangiectasia and Rad-related kinase (ATR). ATR regulates the S-phase checkpoint through phosphorylation of the downstream target structural maintenance of chromosomal protein 1. Furthermore, the ATPase activity of Rad17 is crucial for its chromatin association and for the functional effects of ATR activation in response to low-dose UV radiation. These results suggest that low-dose UV radiation activates an S-phase checkpoint requiring ATR-mediated signal transduction pathway.
Garg
Renu
R
Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, Room 406, CSRB Building, 533 Bolivar Street, New Orleans, LA 70112, USA.
Callens
Shannon
S
Lim
Dae-Sik
DS
Canman
Christine E
CE
Kastan
Michael B
MB
Xu
Bo
B
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins; D002110:Caffeine / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects / Q000528:radiation effects*; D014466:Ultraviolet Rays; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000098550:Structural Maintenance of Chromosome Protein 1; D002110:Caffeine; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases