Work in our laboratory is focused on understanding the molecular transactions that govern chromosome stability and replication. The association of cancer predisposition and other pathology with mutations that affect chromosomal metabolism forms the basis of our interest in this process. In this regard, we focus on a conserved multiprotein complex that includes Mre11, Rad50, and Nbs1 in mammals or Xrs2 in the budding yeast S. cerevisiae. Our laboratory has isolated and characterized the human Mre11 complex, hMre11, hRad50, and Nbs1. We proved that an analogue of the S. cerevisiae Mre11 complex exists in human cells, and subsequently established definitive evidence that the yeast and human complexes mediate double-strand break repair in S. cerevisiae and mammalian cells, respectively. Our data suggest that in human cells, the complex acts as a sensor of DNA damage that participates in the activation of cell cycle checkpoints following g-irradiation.
John Petrini, PhD
Director, The Functional Genomics Initiative
Research FocusMolecular biologist John Petrini investigates the repair of chromosomal breaks and the activation of the DNA-damage-induced cell-cycle checkpoints.
- Dolganov, G.M., Maser, R.S., Novikov, A., Tosto, L., Chong, S., Bressan, D.A., and Petrini, J.H. (1996). Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair. Mol Cell Biol, 16. 4832-4841.
- Maser, R.S., Monsen, K.J., Nelms, B.E., and Petrini, J.H. (1997). Mre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks. Mol Cell Biol, 17. 6087-6096.