Research Projects

Sexually reproducing organisms undergo a specialized cell division process, called meiosis, to form haploid gametes. Proper chromosome inheritance, to preserve fertility in this process, requires induction of potentially genotoxic, programmed double-stranded DNA breaks (DSBs) followed by repair as crossovers between the parental chromosomes. To maintain genome integrity in the face of DNA damage, checkpoint signalling ensures appropriate repair, cell cycle control or cell death. Central to the DNA damage signalling response, is the transducer checkpoint kinase, Chk2. Chk2 is a Ser/ Thr kinase and . Budding yeast orthologues of Chk2 kinase are Rad53 and the meiosis-specific Mek1. While all Chk2 kinases promote homologous recombination-mediated repair of DNA breaks, Mek1 kinase uniquely promotes a biased repair of meiotic DSBs with the homologous chromosome as opposed to repair with the sister chromatid. Additionally all Chk2 kinases regulate G2-M transition of cell cycle in the presence of unrepaired DNA damage. While several groups have investigated how Chk2 and Rad53 are activated, information about molecular mechanism of Mek1 activation is minimal. While few Mek1 substrates have been identified, how Mek1 enforces homologue-biased repair is still not understood. Finally, Chk2 roles have not been identified for exit from M phase in the absence of DNA damage. Our unpublished findings reveal a novel, kinase-independent role of Mek1 in meiosis I – meiosis II transition.