AI Article Synopsis
- The study focuses on identifying the substrates of DNA damage checkpoint kinases (Mec1, Tel1, and Rad53) in yeast, which are similar to human ATR, ATM, and CHK2.
- Using quantitative phosphoproteomics, researchers found 62 phosphorylation sites from 55 proteins regulated by these kinases during genotoxic stress, analyzing nearly 2,700 phosphorylation sites in different cell types.
- In addition to confirming several known targets, the research revealed 50 new targets, indicating that these kinases influence a broad range of cellular processes beyond what was previously understood.
Article Abstract
Understanding the role of DNA damage checkpoint kinases in the cellular response to genotoxic stress requires the knowledge of their substrates. Here, we report the use of quantitative phosphoproteomics to identify in vivo kinase substrates of the yeast DNA damage checkpoint kinases Mec1, Tel1, and Rad53 (orthologs of human ATR, ATM, and CHK2, respectively). By analyzing 2,689 phosphorylation sites in wild-type and various kinase-null cells, 62 phosphorylation sites from 55 proteins were found to be controlled by the DNA damage checkpoint. Examination of the dependency of each phosphorylation on Mec1 and Tel1 or Rad53, combined with sequence and biochemical analysis, revealed that many of the identified targets are likely direct substrates of these kinases. In addition to several known targets, 50 previously undescribed targets of the DNA damage checkpoint were identified, suggesting that a wide range of cellular processes is likely regulated by Mec1, Tel1, and Rad53.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1965519 | PMC |
| http://dx.doi.org/10.1073/pnas.0701622104 | DOI Listing |
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