Nancy Kleckner
Chromosomes

Our laboratory studies chromosomes. We are particularly interested in higher order processes that involve the integration of spatial, temporal and functional elements and in viewing chromosomes as physical objects for which mechanical forces (stresses) play important roles. We study meiotic chromosomes in budding yeast and the filamentous fungus Sordaria with respect to the several steps of homolog recognition and juxtaposition, functional interplay between chromatin and structural axes along and between chromosomes and programmed spatial patterning of interhomolog crossovers. We also use budding yeast to study somatic pairing of homologs and ATR-mediated regulation of DNA replication progression and initiation. A complementary set of studies utilizes E. coli as a model organism. Using our recently-developed "baby cell column" for obtaining large synchronously growing cell populations, we are investigating several aspects which can serve as models for corresponding eukaryotic processes: sister cohesion and loss of cohesion; three-dimensional chromosome disposition; control of replication initiation in coordination with cell division; and mid-cell division site selection. Finally, to begin to analyze chromosomes as mechanical objects, we are investigating the nature and basis of chromosome motion in both yeast meiosis and E.coli; are developing novel single-molecule approaches to investigate the possibility that repeated protein motifs (e.g. the HEAT repeat domains of PIKKs) function as molecular springs; and, in collaboration with the Prentiss group in the Department of Physics, are developing approaches for studying the mechanical properties of intact chromatin and chromosomes inside and outside of cells.

Publications:

Bates, D. and Kleckner, N. 2005. Chromosome and replisome dynamics in E.coli: loss of sister cohesion promotes global chromosome movement and mediates chromosome segregation. Cell 121: 899-911.

N. Kleckner et al. 2004. A mechanical basis for chromosome function. Proc. Natl. Acad. Sci. USA 101: 12592-12597.

Boerner, G.V., Kleckner, N. and Hunter, H. 2004. Crossover/noncrossover differentiation, synaptonemal complex formation and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117: 29-45.

Perry, J. and Kleckner, N. 2003. The ATRs, ATMs, and TORs are giant HEAT repeat proteins. Cell 112: 151-155.

Tessé, S., Storlazzi, A., Kleckner, N., Gargano, S. and Zickler, D. 2003. Localization and roles of Ski8p in Sordaria macrospora meiosis and delineation of three mechanistically distinct steps of meiotic homolog juxtaposition. Proc. Natl. Acad. Sci. USA 100: 12865-12870.

Cha, R.S. and Kleckner, N. 2002. ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones. Science 297: 602-6.

Dekker, J., Rippe, K., Dekker, M. and Kleckner, N. 2002. Capturing Chromosome Conformation Science 295: 1306-1311.

Blat, Y., Protacio, R., Hunter, N. and Kleckner, N. 2002. Physical and functional interactions among basic chromosome organizational features govern early steps of meiotic chiasma formation. Cell 111: 791-802.

Chalmers, R., Guhathakurta, A., Benjamin, H. and Kleckner, N. 1998. IHF modulation of Tn10 transposition: sensory transduction of supercoiling status via a proposed protein/DNA molecular spring. Cell 93: 897-908.

Kleckner, N. and Weiner, B.M. 1993. Potential advantages of unstable interactions for pairing of chromosomes in meiotic, somatic and premeiotic cells. Cold Spring Harbor Symp. Quant. Biol. 58: 553-565.