Publication:
Characterisation of the sites of DNA damage-induced 53BP1 phosphorylation catalysed by ATM and ATR (2007)
Author(s): Jowsey P, Morrice NA, Hastie CJ, McLauchlan H, Toth R, Rouse J
Abstract: The 53BP1 tumour suppressor, an important regulator of genome stability, is phosphorylated in response to ionising radiation (IR) by the ATM protein kinase, itself an important regulator of cellular responses to DNA damage. The only known sites of phosphorylation in 53BP1 are Ser25 and/or Ser29 but 53BP1 lacking these residues is still phosphorylated after DNA damage. In this study, we use mass spectrometry-based together with bioinformatic analysis to identify novel DNA damage-regulated sites of 53BP1 phosphorylation. Several new sites were identified that conform to the consensus Ser/Thr-Gln motif phosphorylated by ATM and related kinases. Phospho-specific antibodies were raised, and were used to demonstrate ATM-dependent phosphorylation of these residues in 53BP1 after exposure of cells to IR. Surprisingly, 53BP1 was also phosphorylated on these residues after exposure of cells to UV light. In this case, 53BP1 phosphorylation did not require ATM but required ATR instead. These data reveal that 53BP1 is phosphorylated on multiple residues in response to different types of DNA damage, and that 53BP1 is regulated by ATR in response to UV-induced DNA damage.
- Type of Article: Brief report
- Date: 05-06-2007
- Journal: DNA Repair
- Volume: 6
- Issue: 10
- Pages: 1536-44
- Publisher: Elsevier BV
- Publication type: Article
- Bibliographic status: Published
- Author Address: MRC Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, Dundee, Scotland, UK.
- URL: http://dx.doi.org/10.1016/j.dnarep.2007.04.011
- DOI: 10.1016/j.dnarep.2007.04.011
- ISSN (electronic): 1568-7856
Keywords: Amino Acid Sequence Catalysis Cell Cycle Proteins/ metabolism Cell Line DNA Damage DNA-Binding Proteins/ metabolism Humans Intracellular Signaling Peptides and Proteins/chemistry/ metabolism Mass Spectrometry Molecular Sequence Data Phosphorylation Protein-Serine-Threonine Kinases/ metabolism Sequence Homology, Amino Acid Tumor Suppressor Proteins/ metabolism Ultraviolet Rays
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Dr Paul Jowsey
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