The differential extension in dsDNA bound to Rad51 filaments may play important roles in homology recognition and strand exchange.

Citation:

Danilowicz C, Peacock-Villada A, Vlassakis J, Facon A, Feinstein E, Kleckner N, Prentiss M. The differential extension in dsDNA bound to Rad51 filaments may play important roles in homology recognition and strand exchange. Nucleic Acids Res. 2013.

Date Published:

2013 Sep 30

Abstract:

RecA and Rad51 proteins play an important role in DNA repair and homologous recombination. For RecA, X-ray structure information and single molecule force experiments have indicated that the differential extension between the complementary strand and its Watson-Crick pairing partners promotes the rapid unbinding of non-homologous dsDNA and drives strand exchange forward for homologous dsDNA. In this work we find that both effects are also present in Rad51 protein. In particular, pulling on the opposite termini (3' and 5') of one of the two DNA strands in a dsDNA molecule allows dsDNA to extend along non-homologous Rad51-ssDNA filaments and remain stably bound in the extended state, but pulling on the 3'5' ends of the complementary strand reduces the strand-exchange rate for homologous filaments. Thus, the results suggest that differential extension is also present in dsDNA bound to Rad51. The differential extension promotes rapid recognition by driving the swift unbinding of dsDNA from non-homologous Rad51-ssDNA filaments, while at the same time, reducing base pair tension due to the transfer of the Watson-Crick pairing of the complementary strand bases from the highly extended outgoing strand to the slightly less extended incoming strand, which drives strand exchange forward.

Key Publications by Subject Area

Chromosomes as Mechanical Objects

• 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.

• 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)

Mammalian chromosome dynamics

• 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.

E.coli chromosome dynamics

• 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.

• 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.

Meiotic Crossover Interference

• 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.

• 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. doi: 10.1073/pnas.1416411111.

• Wang, S., Zickler, D., Kleckner, N. and Zhang, L. 2015. Meiotic crossover patterns: obligatory crossover, interference and homeostasis in a single process. Cell Cycle, 14(3): 305-314.

Homologous Chromosome Pairing

• Zickler, D. and Kleckner, N. 2015. 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) Cold Spring Harb Perspect Biol 2015;7:a016626 doi: 10.1101/CSHPERSPECT.a016626.

• Gladyshev E. and Kleckner, N. 2014. Direct recognition of homology between double helices of DNA in Neurospora crassa. Nat. Commun. 5: 3509 doi: 10.1038/ncomms4509.

• Mirkin, E.V., Chang, F. S. and Kleckner, N. 2013. Dynamic trans interactions in yeast chromosomes. PLoS One 8(9): e75895. doi:10.1371/journal.pone.0075895

• Danilowicz, C., Lee, C.H., Kim K., Hatch, K., Coljee, V.W., Kleckner, N. and Prentiss, M. 2009. Single molecule detection of direct, homologous DNA/DNA pairing. Proc. Natl. Acad. Sci. USA, 106, 19,824-19,829.

• Weiner, B.M. and Kleckner, N. 1994. Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast. Cell 77: 977-991.

• Burgess, S.M., Kleckner, N. and Weiner, B.M. 1999. Somatic pairing of homologs in budding yeast: existence and modulation. Genes Dev. 13, 1627-1641.

• 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.

Meiotic Sordaria Chromosomes

• De Muyt A, Zhang, L., Piolot, T., Kleckner, N., Espagne,, E. and Zickler D. 2014. E3 ligase Hei10: a multi-faceted structure-based signaling molecule with roles within and beyond meiosis. Genes Dev 28: 1111-1123.

• 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.

Nancy Kleckner

Herchel Smith Professor of Molecular Biology

The differential extension in dsDNA bound to Rad51 filaments may play important roles in homology recognition and strand exchange.

Citation:

Date Published:

Abstract:

Key Publications by Subject Area