Building bridges to move recombination complexes

Citation:

Dubois E, De Muyt A, Soyer JL, Budin K, Legras M, Piolot T, Debuchy R, Kleckner N, Zickler D, Espagne E. Building bridges to move recombination complexes. Proc Natl Acad Sci U S A. 2019;116 (25) :12400-12409.

Date Published:

2019 Jun 18

Abstract:

A central feature of meiosis is pairing of homologous chromosomes, which occurs in two stages: coalignment of axes followed by installation of the synaptonemal complex (SC). Concomitantly, recombination complexes reposition from on-axis association to the SC central region. We show here that, in the fungus , this critical transition is mediated by robust interaxis bridges that contain an axis component (Spo76/Pds5), DNA, plus colocalizing Mer3/Msh4 recombination proteins and the Zip2-Zip4 mediator complex. Mer3-Msh4-Zip2-Zip4 colocalizing foci are first released from their tight axis association, dependent on the SC transverse-filament protein Sme4/Zip1, before moving to bridges and thus to a between-axis position. Ensuing shortening of bridges and accompanying juxtaposition of axes to 100 nm enables installation of SC central elements at sites of between-axis Mer3-Msh4-Zip2-Zip4 complexes. We show also that the Zip2-Zip4 complex has an intrinsic affinity for chromosome axes at early leptotene, where it localizes independently of recombination, but is dependent on Mer3. Then, later, Zip2-Zip4 has an intrinsic affinity for the SC central element, where it ultimately localizes to sites of crossover complexes at the end of pachytene. These and other findings suggest that the fundamental role of Zip2-Zip4 is to mediate the recombination/structure interface at all post-double-strand break stages. We propose that Zip2-Zip4 directly mediates a molecular handoff of Mer3-Msh4 complexes, from association with axis components to association with SC central components, at the bridge stage, and then directly mediates central region installation during SC nucleation.

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

Building bridges to move recombination complexes

Citation:

Date Published:

Abstract:

Key Publications by Subject Area