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Stiff, Thomas, Walker, Sarah A, Cerosaletti, Karen, Goodarzi, Aaron A, Petermann, Eve, Concannon, Pat, O'Driscoll, Mark and Jeggo, Penny A (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 0261-4189
Full text not available from this repository.Abstract
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. ATRdependent 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.
| Item Type: | Article |
|---|---|
| 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 |
| Related URLs: | |
| Depositing User: | Gee Wheatley |
| Date Deposited: | 15 Feb 2008 |
| Last Modified: | 12 Feb 2019 14:35 |
| URI: | http://sro.sussex.ac.uk/id/eprint/726 |
| Google Scholar: | 146 Citations |