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
Chair, Molecular Biology Program, SKI; 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.
EducationPhD, University of Michigan Medical School
- Balestrini, A., Ristic, D., Dionne, I., Liu, X., Wyman, C., Wellinger, R.C., Petrini, J.H. (2013) The Ku heterodimer and the metabolism of single-ended DNA double strand breaks. Cell Reports, 3. 2033-45. PMCID: PMC3815622
- Ballew, B., Joseph, V., De, S., Sarek, G., Vannier, J-B., Stracker, T., Schrader, K.A., Small, T.N., O’Reilly, R., Manschreck, C., Harlan Fleischut, M.M., Sullivan, J., Stratton, K., Yeager, M., Jacobs, K., Giri, N., Alter, B.P., Boland, J., Burdett, L., Offit, K., Boulton, S., Savage, S.A., Petrini, J.H.J. (2013) A Recessive Founder Mutation in Regulator of Telomere Elongation Helicase 1, RTEL1, Underlies Severe Immunodeficiency and Features of Hoyeraal Hreidarsson Syndrome. PLoS Genetics, 8.: e1003695 PMCID: PMC3757051