Chromosomes as Mechanical Objects
We wish to provide descriptions of global chromosomal processes from an entirely new perspective in which chromosomes are considered as mechanical objects. In this view, important fundamental features of chromosomal processes are manifestations of the accumulation, release and redistribution of mechanical forces (stresses) within/along/between/among chromosomes and sub-chromosomal domains. An alternative, but equivalent, way of stating this idea is that chromosomal events will be described and analyzed as manifestations of the nature and dynamics of the mechanical energy landscape.
To this end, we study chromosomal events in vivo, in real time, in normal and perturbed situations. We are developing new imaging and force-sensing tools as required for such research (currently unpublished). We are applying these and other tools to chromosomal systems ranging from bacteria (E.coli) to worms (C.elegans) to mammalian cells (human, mouse and muntjac) and, in eukaryotes, both mitotic and meiotic cellular programs. These studies have revealed, and continue to reveal, commonalities among all of the analyzed systems, all fundamentally grounded in the basic nature of DNA as the genetic material.
We welcome new laboratory members who wish to apply quantitative methods from physics and engineering to fundamental chromosomal processes.
Kleckner, N., Zickler, D., Jones, G.H., Henle, J., Dekker, J. and Hutchinson, J. 2004. A mechanical basis for chromosome function. Proc. Natl. Acad. Sci. USA, 101, 12592-12597.
Grinthal, A., Adamovic, I., Weiner, B., Karplus, M. and Kleckner, N. 2010. PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis. Proc. Natl. Acad. Sci., USA, 107, 2467-2472.
Storlazzi, A., Gargano, S., Ruprich-Robert, G., Falque, M., David, M., Kleckner, N. and Zickler, D. 2010. Recombination proteins mediate meiotic spatial chromosome organization and pairing. Cell 141 94-106.
Fisher, J.K., Bourniquel, A., Witz, G., Weiner, B., Prentiss, M. and Kleckner, N. 2013. Four-dimensional imaging of E. coli organization and dynamics in living cells. Cell 153, 882-895.
Zhang, L., Wang, S., Yin, S., Hong, S. Kim, K.P. and Kleckner, N. 2014. Topoisomerase II mediates meiotic crossover interference. Nature 511: 551-556.
Fisher, J.K. and Kleckner, N. 2014. Magnetic Force Micropiston: an integrated force microfluidic device for the application of compressive forces in a confined environment. Rev. Sci. Instrum. 85 023704 (2014); http://dx.doi.org/10.1063/1.4864085, (issue date Feb. 14, 2014).
Zhang, L, Espagne, E., De Muyt, A., Zickler, D. and Kleckner, N. 2014. Interference-mediated synaptonemal complex formation with embedded crossover-designation. Proc. Natl. Acad. Sci. U.S.A. 111(47):E5059-68.
Liang, Z., Zickler, D., Prentiss, M., Chang, F.S., Witz, G., Maeshima, K. and Kleckner, N. 2015. Chromosomes progress to metaphase in multiple discrete steps via global compaction/expansion cycles. Cell 161: 1124-1137.
White, M., Wang, S., Zhang, L. and Kleckner, N. 2016. Modeling of meiotic crossover interference as inspired by the beam-film model. In Stuart, D.T., Meiosis, Second ed. (New York, NY, Humana Press), Meth. Mol. Biol. 1471, in press.
Gladyshev E. and Kleckner, N. 2014. Direct recognition of homology between double helices of DNA in Neurospora crassa. Nat. Commun. 5: 3509.
Kleckner, N., Fisher, J.K., Stouf, M., White, M.A., Bates, D. and Witz, G. 2014. The bacterial nucleoid: nature, dynamics and sister segregation. Curr. Opin. Microbiol. 22: 127-137.
Zickler, D. and Kleckner, N. 2016. Recombination, pairing and synapsis of homologs in meiosis. In Kowalczykowski, S., Hunter, N. and Heyer, W.-D., DNA Replication (Cold Spring Harbor: Cold Spring Harbor Press).
Kleckner, N. 2016. Questions and Assays. Genetics 204(4): 1343-1349. Essay solicited by the Genetics Society of America in conjunction with the GSA’s Thomas Hunt Morgan Lifetime Achievement Award, 2016.