ATR kinase as master regulator of nucleotide excision repair during S phase of the cell cycle.
Nucleotide excision repair (NER) is a major determinant in cancer development and treatment via its essential role in eliminating highly-genotoxic, helix-distorting DNA adducts that block replication and transcription. Over the years, many elegant studies employing UV as model mutagen have led to a detailed understanding of how the NER pathway itself is coordinated. Nonetheless relatively little is known regarding any precise functions of various preeminent mutagen-responsive signaling cascades lying upstream of NER, notably those mediated by the canonical MAPKs or the PIKK family members ATR and ATM. Here we present a brief overview of NER, mostly in the context of studies on human cells treated with UV, and describe recent results from our laboratory which have significantly elucidated the role of UV-induced signal transduction in this repair pathway.
Department of Immunology/Oncology, Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Montreal, QC, Canada.
Yannick
Y
Auclair
Raphael
R
Rouget
Elliot A
EA
Drobetsky
D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016196:S Phase; D015398:Signal Transduction / Q000502:physiology*
D018797:Cell Cycle Proteins; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases