Stiff, Thomas, Walker, Sarah, Cerosaletti, Karen, Goodarzi, Aaron, Petermann, Mylene Pamela, Concannon, Pat, O'Driscoll, Mark and Jeggo, Penny (2006) ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO Journal, 25 (24). pp. 5775-5782. ISSN 0261-4189Full text not available from this repository.
The phosphatidyl inositol 3-kinase-like kinases (PIKKs), ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) regulate parallel damage response signalling pathways. ATM is reported to be activated by DNA double-strand breaks (DSBs), whereas ATR is recruited to single-stranded regions of DNA. Although the two pathways were considered to function independently, recent studies have demonstrated that ATM functions upstream of ATR following exposure to ionising radiation (IR) in S/G2. Here, we show that ATM phosphorylation at Ser1981, a characterised autophosphorylation site, is ATR-dependent and ATM-independent following replication fork stalling or UV treatment. In contrast to IR-induced ATM-S1981 phosphorylation, UV-induced ATM-S1981 phosphorylation does not require the Nbs1 C-terminus or Mre11. ATR-dependent phosphorylation of ATM activates ATM phosphorylation of Chk2, which has an overlapping function with Chk1 in regulating G2/M checkpoint arrest. Our findings provide insight into the interplay between the PIKK damage response pathways.
|Keywords:||Ataxia telangiectasia-mutated protein, DNA damage responses, phosphorylation, PIKKs|
|Schools and Departments:||School of Life Sciences > Biochemistry|
|Subjects:||Q Science > QD Chemistry
Q Science > QH Natural history > QH0301 Biology
|Depositing User:||Gee Wheatley|
|Date Deposited:||15 Feb 2008|
|Last Modified:||17 Jul 2012 11:22|
|Google Scholar:||146 Citations|