Contact Information

University Of Illinois at Chicago

Dept. Of Biochemistry and

Molecular Genetics

900 S. Ashland (M/C 669)
Chicago, IL 60607
tel: 312-996-7670
fax: 312-413-0353

A model of G2/M DNA damage checkpoint in fission yeast

We use fission yeast Schizosaccharomyces pombe as a major model system. Advantages of S. pombe include well-characterized DNA damage responses with high structural and functional conservation to mammalian cells, and amenability to genetic, biochemical and cytological studies. In addition, the ability of fission yeast to bypass the need for functional telomere maintenance mechanism by circularizing all chromosomes provides flexibility, not available in any other organisms, in manipulating telomere related genes without being hindered by cell lethality. In fact, S. pombe cells lacking telomerase, as well as cells lacking both Tel1 and Rad3 kinases, have three circular chromosomes. We are also taking advantage of information gained from the completed S. pombe genome sequence to guide our experiments. Given the highly conserved underlining mechanisms of checkpoints and DNA repair, insights gained from S. pombe studies are expected to help guide future cancer research in mammalian cells.

Selected Publications:

Subramanian, L., Moser, B.A., Nakamura, T.M. (2008) Recombination-based telomere maintenance is dependent on Tel1-MRN and Rap1, and inhibited by telomerase, Taz1 and Ku in fission yeast. Mol. Cell. Biol. 28:1443-1455.

Ansbach, A.B., Noguchi, C., Klansek, I.W., Heidlebaugh, M., Nakamura, T.M., Noguchi, E. (2008) RFCCtf18 and the Swi1-Swi3 complex function in separate and redundant pathways required for the stabilization of replication forks to facilitate sister chromatid cohesion in Schizosaccharomyces pombe. Mol. Biol. Cell 19:595-607.

Du, L.-L., Nakamura, T.M., Russell, P. (2006) Histone modification-dependent and -independent pathways for recruitment of checkpoint protein Crb2 to double-strand breaks. Genes Dev. 20: 1583-1596.

Nakamura, T.M., Moser, B.A., Du, L.-L. & Russell, P. (2005) Cooperative Control of Crb2 by ATM-family and Cdc2 Kinases is Essentail for the DNA Damage Checkpoint in Fission Yeast. Mol. Cell. Biol. 25, 10721-10730.

Nakamura, T.M., Du, L.-L., Redon, C. & Russell, P. (2004) Histone H2A Phosphorylation Controls
Crb2 Recruitment at DNA Breaks, Maintains Checkpoint Arrest, and Influences DNA Repair in Fission Yeast. Mol. Cell. Biol. 24, 6215-6230.

Chahwan, C., Nakamura, T.M., Sivakumar, S., Russell, P., & Rhind, N. (2003) The fission yeast Rad32 (Mre11)-Rad50-Nbs1complex is required for the S-phase DNA checkpoint. Mol. Cell. Biol. 23, 6564-6573.

Du, L.-L., Nakamura, T.M., Moser, B.A., and Russell, P. (2003) Retention but not recruitment of Crb2 at double-strand breaks requires Rad1 and Rad3 complexes. Mol. Cell. Biol. 23, 6150-6158.

Nakamura, T.M., Moser, B.A., and Russell, P. (2002) Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres. Genetics 161, 1437-1452.

Haering, C.H., Nakamura, T.M., Baumann, P., and Cech, T.R. (2000) Analysis of telomerase catalytic subunit mutants in vivo and in vitro in Schizosaccharomyces pombe. Proc. Natl. Acad. Sci. USA. 97, 6367-6372.

Nakamura, T.M., Cooper, J.P., and Cech, T.R. (1998) Two modes of survival of fission yeast without telomerase. Science 282, 493-496.

Nakamura, T.M. and Cech, T.R. (1998) Reversing time: origin of telomerase. Cell 92, 587-590.

Nakamura, T.M., Morin, G.B., Chapman, K.B., Weinrich, S.L., Andrews, W.H., Lingner, J., Harley, C.B., Cech, T.R. (1997) Telomerase catalytic subunit homologs from fission yeast and human. Science 277, 955-959.