How ATR turns on: TopBP1 goes on ATRIP with ATR.
In this issue of Genes & Development, Mordes and colleagues (pp. 1478-1489) reveal intriguing mechanistic insights into activation of the ATR (ATM and Rad3-related) kinase critical for DNA damage resistance. They identify conserved regulatory domains within ATR and its binding partner ATRIP (ATR-interacting protein), which are contacted by the ATR activator TopBP1. These discoveries expand on our understanding of the regulation of other PIKK family members, which also contain these domains, and illustrate how functional diversity has been achieved among these kinases.
Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Anna E
AE
Burrows
Stephen J
SJ
Elledge
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017124:Conserved Sequence; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
C521194:ATRIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110513:TOPBP1 protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases