Crossover Interference, Crossover Maturation, and Human Aneuploidy

Citation:

Wang S, Liu Y, Shang Y, Zhai B, Yang X, Kleckner N, Zhang L. Crossover Interference, Crossover Maturation, and Human Aneuploidy. Bioessays. 2019;41 (10) :e1800221.

Date Published:

2019 Oct

Abstract:

A striking feature of human female sexual reproduction is the high level of gametes that exhibit an aberrant number of chromosomes (aneuploidy). A high baseline observed in women of prime reproductive age is followed by a dramatic increase in older women. Proper chromosome segregation requires one or more DNA crossovers (COs) between homologous maternal and paternal chromosomes, in combination with cohesion between sister chromatid arms. In human females, CO designations occur normally, according to the dictates of CO interference, giving early CO-fated intermediates. However, ≈25% of these intermediates fail to mature to final CO products. This effect explains the high baseline of aneuploidy and is predicted to synergize with age-dependent cohesion loss to explain the maternal age effect. Here, modern advances in the understanding of crossing over and CO interference are reviewed, the implications of human female CO maturation inefficiency are further discussed, and areas of interest for future studies are suggested.

Key Publications by Subject Area

Chromosomes as Mechanical Objects

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• 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.

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• 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

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• 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

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• 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

Crossover Interference, Crossover Maturation, and Human Aneuploidy

Citation:

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Key Publications by Subject Area