Nancy E. Kleckner, Ph.D.
Professor of Biochemistry and Molecular Biology
Harvard University
Fairchild Bldg., Rm. 301
7 Divinity Ave.
Cambridge, MA 02138
Tel: 617-495-4278
Fax: 617-495-8308
e-mail:kleckner@fas.harvard.edu
13 postdoctoral fellows, 2 graduate students
We analyze chromosome function by genetic, biochemical, molecular and cytological methods.
- Meiosis in S.cerevisiae. Successful meiosis requires that homologous chromosomes recognize and pair with one another and undergo recombination, not only within the DNA but between the underlying involved chromatid axes. These local events are spatially, temporally and functionally coordinated with global changes along chromosomes and in overall chromosome disposition. We are investigating all of these processes and their relationships. Of special interest are DSB-independent pairing, regulation of crossover position (crossover interference), the roles of sister chromatid relationships and the role of the meiotic "bouquet stage" when telomeres become spatially localized opposite the spindle pole body.
- We have developed a mechanical model for chromosome function. In brief, we propose programmed chromatin expansion against constraining features generates mechanical stress and that such stress governs many chromosome activities. Mechanical experiments to test this hypothesis are under development.
- Coordination of the DNA replication and cell division "cycles" of E. coli. We investigate functional links amongst replication initiation, termination and chromosome segregation using our newly developed "baby cell" machine for generating synchronous bacterial cell populations in combination with FISH, immunofluorescence and FACS analysis. We think that the E.coli replicatoin/cell division cycle may be a "stripped-down" version of its eukaryotic counterpart which therefore manifests certain underlying features of the eukaryotic program that are normally obscured by overlaid additional features.
- Chromosome-based signal transduction (e.g. Mec1/ATR). We find that Mec1, yeast homolog of mammalian chromosome-based signal transduction protein ATR, plays an essential role in promoting replication progression irrespective of incidental chromosomal damage. We are further exploring the nature of this activity and of Mec1 and ATR function in general by functional and biochemical approaches.
References:
- Cha, R.S. and Kleckner, N. 2002. Roles of ATR-Homolog Mec1 in Replication Fork Progression and Prevention of Chromosome Breakage in Replication Slow Zones. Science (in press). Dekker, J., Rippe, K., Dekker, M. and Kleckner, N. 2002. Capturing Chromosome Conformation. Science 295: 1306-1311.
- Blat Y, Protacio RU, Hunter N, Kleckner N. Physical and functional interactions among basic chromosome organizational features govern early steps of meiotic chiasma formation.
- Kleckner, N., Zickler, D., Jones, G.H., Henle, J., Dekker, J. and Hutchinson J. A mechanical model for chromosome function. PNAS in press.
- Borner GV, Kleckner N, Hunter N. Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell. 2004 Apr 2;117(1):29-45.
Virology webpage updated 12/02/2009