Harvard University - Department of Molecular & Cellular Biology

NANCY KLECKNER

Kleckner
Herchel Smith Professor of Molecular Biology

Email: kleckner@fas.harvard.edu
Phone: 617-495-4278

Mail: NW 140.05
Northwest Building
52 Oxford St
Cambridge, MA  02138

Kleckner Lab Website
Engineering and Physical Biology (EPB)
Members of the Kleckner Lab
List of Publications from PubMed

Courses

MCB 144. The Power and Pitfalls of Genetical Thinking
Catalog Number: 25555  View Course Website
Term: [Spring Term 2014-2015.]   Credit: Half course.
Instructors: David Haig, Nancy Kleckner
Course Level: For Undergraduates and Graduates
Description: An advanced treatment of heredity, including genetic, epigenetic and evolutionary aspects, as manifested in organisms from bacteria to man. Emphasis will be placed on how analytical genetic thinking and approaches can be applied to fundamental biological questions. Course format will include lectures, reading of the primary literature, student group projects and a final paper. Suitable for students in either the physical or biological sciences.
Meetings: M., W., 12-1:30
MCB 188. Chromosomes
Catalog Number: 8561  View Course Website
Term: Spring Term 2013-2014.   Credit: Half course.
Instructor: Nancy Kleckner
Course Level: For Undergraduates and Graduates
Description: Chromosome morphogenesis in prokaryotic and eukaryotic organisms. Topics will include chromosome structure, interactions between chromosomes (sisters and homologs), DNA recombination and repair, topoisomerases, transposable elements and site-specific recombination, epigenetic inheritance. Genetic, cytological, and biochemical approaches will be integrated. Lecture, reading, and discussion of classical and current literature and consideration of future experimental directions.
Prerequisite(s): Life Sciences 1b or equivalent, MCB 52, and MCB 54.
Meetings: Tu., Th., 2-4
MCB 294. Interesting Questions in Engineering and Physical Biology
Catalog Number: 7646  View Course Website
Term: Fall Term 2013-2014.   Credit: Half course.
Instructors: Nancy Kleckner, Mara Prentiss
Course Level: Primarily for Graduates
Description: Physical biology can be defined as a discipline that seeks to understand biological processes through the lens of physics and engineering. Faculty and students will unite to review current research with the aim of identifying and pondering interesting emerging questions in this area. Combination of lecture and discussion format. Comprises a series of two-week modules, most of which are given by a one or a pair of faculty drawn from MCB, Physics and SEAS.
Note: Intended primarily for first year graduate students in the EPB PhD track of the MCO program but available to other graduate students and advanced undergraduates as space permits.
Meetings: Tu., Th., 1-2:30
MCB 359. Chromosomes
Catalog Number: 6278  View Course Website
Term: Fall Term; Repeated Spring Term 2013-2014.   Credit: Half course.
Instructor: Nancy Kleckner
Course Level: Graduate Course
BIOPHYS 321. Molecular and Mechanical Analysis of Chromosomes
Catalog Number: 7297  View Course Website
Term: Fall Term; Repeated Spring Term 2013-2014.   Credit: Half course.
Instructor: Nancy Kleckner
Course Level: Graduate Course
ENG-SCI 224. Laboratory in Engineering and Physical Biology
Catalog Number: 4136  View Course Website
Term: Spring Term 2013-2014.   Credit: Half course.
Instructors: Nancy Kleckner, Mara Prentiss
Course Level: Primarily for Graduates
Description: A project-oriented laboratory course which will integrate genetic, molecular, biochemical and cytological approaches from the life sciences with optical, magnetic and mechanical approaches from the physical sciences. Interesting and original experiments will be organized around a common theme which, this year, will be "Biomechanics of E. coli."
Note: Intended primarily for first year graduate students in the EPB PhD track but available to other graduate students and advanced undergraduates as space and resources permit.
Meetings: M., W., 1-5
VIROLOGY 307. Genetics and Biochemistry of Prokaryotic Transposable Elements and Yeast Meiotic Chromosome Metabolism
Catalog Number: 6097  View Course Website
Term: Fall Term; Repeated Spring Term 2013-2014.   Credit: Half course.
Instructor: Nancy Kleckner
Course Level: Graduate Course
(View all MCB Courses)

Research

Chromosome dynamics underlie the transmission of genetic information from generation to generation. From this perspective, we compare and contrast events in E.coli and during mitosis and meiosis in eukaryotic cells including in budding yeast, filamentous fungi and mammalian cells. We are interested in both biological and physical biological issues. Our experiments involve classical approaches (genetics, biochemistry, molecular biology); high-resolution 4D imaging; micromechanical and single molecule manipulation; molecular dynamics simulations; and mathematical analysis.

Current research topics include: E.coli nucleoid dynamics; mammalian mitotic chromosome morphogenesis; physical analysis of meshwork chromatin expansion stress as a driving force for chromosomal changes; recombination-independent pairing of homologous chromosomes in yeast and Neurospora and in vitro; spatial patterning of crossover sites along meiotic chromosomes in yeast and Sordaria; DNA/structure interplay and sister/homolog partner choice during meiotic recombination in yeast and Sordaria; and 4D (spatio-temporal) patterns of chromosome and double-strand break movement during meiosis in yeast.

Integral to this work are close collaborations with the laboratories of Denise Zickler (U. Paris-Sud; http://www.igmors.u-psud.fr/spip.php?article892&lang=en); Mara Prentiss (Harvard Department of Physics; http://prentiss.physics.harvard.edu/) and John Hutchinson (Harvard School of Engineering and Applied Sciences; http://www.seas.harvard.edu/hutchinson/).

Publications

Kleckner, N, Zickler, D, Jones, GH, Dekker, J, Padmore, R, Henle, J, and Hutchinson, J. (2004) A mechanical basis for chromosome function. Proc. Natl. Acad. Sci. U.S.A., 101(34):12592-7. PMID: 15299144  PMC515102

Koszul, R, Kim, KP, Prentiss, M, Kleckner, N, and Kameoka, S. (2008) Meiotic chromosomes move by linkage to dynamic actin cables with transduction of force through the nuclear envelope. Cell, 133(7):1188-201. PMID: 18585353  PMC2601696

Danilowicz, C, Lee, CH, Kim, K, Hatch, K, Coljee, VW, Kleckner, N, and Prentiss, M. (2009) Single molecule detection of direct, homologous, DNA/DNA pairing. Proc. Natl. Acad. Sci. U.S.A., 106(47):19824-9. PMID: 19903884  PMC2775704

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. U.S.A., 107(6):2467-72. PMID: 20133745  PMC2823866

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(1):94-106. PMID: 20371348  PMC2851631

Kleckner, N. (2010) Mesoscale spatial patterning in the Escherichia coli Min system: reaction-diffusion versus mechanical communication. Proc. Natl. Acad. Sci. U.S.A., 107(18):8053-4. PMID: 20421460  PMC2889530

Conover, AJ, Danilowicz, C, Gunaratne, R, Coljee, VW, Kleckner, N, and Prentiss, M. (2011) Changes in the tension in dsDNA alter the conformation of RecA bound to dsDNA-RecA filaments. Nucleic Acids Res., 39(20):8833-43. PMID: 21768124  PMC3203582

Fisher, JK, Bourniquel, A, Witz, G, Weiner, B, Prentiss, M, and Kleckner, N. (2013) Four-dimensional imaging of E. coli nucleoid organization and dynamics in living cells. Cell, 153(4):882-95. PMID: 23623305  PMC3670778

Hong, S, Sung, Y, Yu, M, Lee, M, Kleckner, N, and Kim, KP. (2013) The logic and mechanism of homologous recombination partner choice. Mol. Cell, 51(4):440-53. PMID: 23973374  

Mirkin, EV, Chang, FS, and Kleckner, N. (2013) Dynamic trans interactions in yeast chromosomes. PLoS ONE, 8(9):e75895. PMID: 24098740  PMC3786970

Zhang, L, Liang, Z, Hutchinson, J, and Kleckner, N. (2014) Crossover patterning by the beam-film model: analysis and implications. PLoS Genet., 10(1):e1004042. PMID: 24497834  PMC3907302

Fisher, JK, 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(2):023704. PMID: 24593368  

Gladyshev E. and Kleckner, N. (2014) Direct recognition of homology between double helices of DNA in Neurospora crassa. Nature Communications, in press.

Zhang, L., Wang, S., Yin, S., Hong, S. Kim, K.P. and Kleckner, N. (2014) Topoisomerase II mediates meiotic crossover interference. Nature, in final revision for publication.

updated: 04/22/2014