Molecular Genetics - PhD and honours Projects - Regulation of cell cycle checkpoint kinases
Regulation of cell cycle checkpoint kinases
Project Type
PhD
Summary
The highly conserved ATM/ATR-like and Chk2-like protein kinase cascade is crucial for cellular signalling responses to DNA damage and the prevention of cancer, but the functional regulation of these kinases is still not completely understood. We have generated a comprehensive set of mutated alleles of the yeast Chk2-like kinase Rad53 that differentially affect Rad53 activation and cellular signalling outcomes. The aim of this project is to take advantage of the simple yeast model organism to decipher the precise molecular mechanisms of how Chk2-like kinases are regulated in response to DNA damage, as well as during normal cell cycles. The project involves a diverse range of approaches from yeast genetic analyses including high-throughput robotics, yeast cell biology, in vitro enzyme assays, and mass spectrometry, and may also involve follow-up studies in mammalian tissue culture systems.
Recent publications: Lee et al, Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade, Molecular Cell 30, 767-778 (2008); Pike & Heierhorst, Mdt1 facilitates efficient repair of blocked DNA double-strand breaks and recombinational maintenance of telomeres, Molecular and Cellular Biology 27, 6532-6545 (2007).