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Phys Biol. 2019 May 7;16(4):046005. doi: 10.1088/1478-3975/ab15a7.

Modeling meiotic chromosome pairing: a tug of war between telomere forces and a pairing-based Brownian ratchet leads to increased pairing fidelity.

Author information

1
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, United States of America. Center for Cellular Construction, University of California San Francisco, San Francisco, CA, United States of America.

Abstract

Meiotic homolog pairing involves associations between homologous DNA regions scattered along the length of a chromosome. When homologs associate, they tend to do so by a processive zippering process, which apparently results from avidity effects. Using a computational model, we show that this avidity-driven processive zippering reduces the selectivity of pairing. When active random forces are applied to telomeres, this drop in selectivity is eliminated in a force-dependent manner. Further simulations suggest that active telomere forces are engaged in a tug-of-war against zippering, which can be interpreted as a Brownian ratchet with a stall force that depends on the dissociation constant of pairing. When perfectly homologous regions of high affinity compete with homeologous regions of lower affinity, the affinity difference can be amplified through this tug of war effect provided the telomere force acts in a range that is strong enough to oppose zippering of homeologs while still permitting zippering of correct homologs. The degree of unzippering depends on the radius of the nucleus, such that complete unzippering of homeologous regions can only take place if the nucleus is large enough to pull the two chromosomes completely apart. A picture of meiotic pairing thus emerges that is fundamentally mechanical in nature, possibly explaining the purpose of active telomere forces, increased nuclear diameter, and the presence of 'Maverick' chromosomes in meiosis.

PMID:
30943453
PMCID:
PMC6581521
DOI:
10.1088/1478-3975/ab15a7
[Indexed for MEDLINE]
Free PMC Article

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