Ataxia-telangiectasia mutated (ATM)-dependent activation of ATR occurs through phosphorylation of TopBP1 by ATM.
ATM (ataxia-telangiectasia mutated) is necessary for activation of Chk1 by ATR (ATM and Rad3-related) in response to double-stranded DNA breaks (DSBs) but not to DNA replication stress. TopBP1 has been identified as a direct activator of ATR. We show that ATM regulates Xenopus TopBP1 by phosphorylating Ser-1131 and thereby strongly ... enhancing association of TopBP1 with ATR. Xenopus egg extracts containing a mutant of TopBP1 that cannot be phosphorylated on Ser-1131 are defective in the ATR-dependent phosphorylation of Chk1 in response to DSBs but not to DNA replication stress. Thus, TopBP1 is critical for the ATM-dependent activation of ATR following production of DSBs in the genome.
Mesh Terms:
Amino Acid Sequence, Animals, Ataxia Telangiectasia Mutated Proteins, Carrier Proteins, Cell Cycle Proteins, DNA Damage, DNA Repair, DNA-Binding Proteins, Enzyme Activation, Humans, Molecular Sequence Data, Oocytes, Phosphorylation, Protein-Serine-Threonine Kinases, Recombinant Proteins, Sequence Alignment, Serine, Tumor Suppressor Proteins, Xenopus Proteins, Xenopus laevis
Amino Acid Sequence, Animals, Ataxia Telangiectasia Mutated Proteins, Carrier Proteins, Cell Cycle Proteins, DNA Damage, DNA Repair, DNA-Binding Proteins, Enzyme Activation, Humans, Molecular Sequence Data, Oocytes, Phosphorylation, Protein-Serine-Threonine Kinases, Recombinant Proteins, Sequence Alignment, Serine, Tumor Suppressor Proteins, Xenopus Proteins, Xenopus laevis
J Biol Chem
Date: Jun. 15, 2007
PubMed ID: 17446169
View in: Pubmed Google Scholar
Download Curated Data For This Publication
232394
Switch View:
- Interactions 7