Multiple Opposing Constraints Govern Chromosome Interactions During Meiosis

Overview

Journal PLoS Genet

Specialty Genetics

Date 2013 Jan 24

PMID 23341780

Citations 13

Authors

Doris Y Lui

Cori K Cahoon

Sean M Burgess

Affiliations

Soon will be listed here.

Abstract

Homolog pairing and crossing over during meiosis I prophase is required for accurate chromosome segregation to form euploid gametes. The repair of Spo11-induced double-strand breaks (DSB) using a homologous chromosome template is a major driver of pairing in many species, including fungi, plants, and mammals. Inappropriate pairing and crossing over at ectopic loci can lead to chromosome rearrangements and aneuploidy. How (or if) inappropriate ectopic interactions are disrupted in favor of allelic interactions is not clear. Here we used an in vivo "collision" assay in budding yeast to test the contributions of cohesion and the organization and motion of chromosomes in the nucleus on promoting or antagonizing interactions between allelic and ectopic loci at interstitial chromosome sites. We found that deletion of the cohesin subunit Rec8, but not other chromosome axis proteins (e.g. Red1, Hop1, or Mek1), caused an increase in homolog-nonspecific chromosome interaction, even in the absence of Spo11. This effect was partially suppressed by expression of the mitotic cohesin paralog Scc1/Mdc1, implicating Rec8's role in cohesion rather than axis integrity in preventing nonspecific chromosome interactions. Disruption of telomere-led motion by treating cells with the actin polymerization inhibitor Latrunculin B (Lat B) elevated nonspecific collisions in rec8Δ spo11Δ. Next, using a visual homolog-pairing assay, we found that the delay in homolog pairing in mutants defective for telomere-led chromosome motion (ndj1Δ or csm4Δ) is enhanced in Lat B-treated cells, implicating actin in more than one process promoting homolog juxtaposition. We suggest that multiple, independent contributions of actin, cohesin, and telomere function are integrated to promote stable homolog-specific interactions and to destabilize weak nonspecific interactions by modulating the elastic spring-like properties of chromosomes.

Citing Articles

Modeling homologous chromosome recognition via nonspecific interactions.

Marshall W, Fung J Proc Natl Acad Sci U S A. 2024; 121(20):e2317373121.

PMID: 38722810 PMC: 11098084. DOI: 10.1073/pnas.2317373121.

Modeling cell biological features of meiotic chromosome pairing to study interlock resolution.

J Navarro E, Marshall W, Fung J PLoS Comput Biol. 2022; 18(6):e1010252.

PMID: 35696428 PMC: 9232156. DOI: 10.1371/journal.pcbi.1010252.

Diffusion and distal linkages govern interchromosomal dynamics during meiotic prophase.

Newman T, Beltran B, McGehee J, Elnatan D, Cahoon C, Paddy M Proc Natl Acad Sci U S A. 2022; 119(12):e2115883119.

PMID: 35302885 PMC: 8944930. DOI: 10.1073/pnas.2115883119.

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

Marshall W, Fung J Phys Biol. 2019; 16(4):046005.

PMID: 30943453 PMC: 6581521. DOI: 10.1088/1478-3975/ab15a7.

The telomere bouquet is a hub where meiotic double-strand breaks, synapsis, and stable homolog juxtaposition are coordinated in the zebrafish, Danio rerio.

Blokhina Y, Nguyen A, Draper B, Burgess S PLoS Genet. 2019; 15(1):e1007730.

PMID: 30653507 PMC: 6336226. DOI: 10.1371/journal.pgen.1007730.

References

Hochwagen A, Tham W, Brar G, Amon A . The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity. Cell. 2005; 122(6):861-73. DOI: 10.1016/j.cell.2005.07.010. View

Conrad M, Dominguez A, Dresser M . Ndj1p, a meiotic telomere protein required for normal chromosome synapsis and segregation in yeast. Science. 1997; 276(5316):1252-5. DOI: 10.1126/science.276.5316.1252. View

Meaburn K, Misteli T, Soutoglou E . Spatial genome organization in the formation of chromosomal translocations. Semin Cancer Biol. 2006; 17(1):80-90. PMC: 1805052. DOI: 10.1016/j.semcancer.2006.10.008. View

Stephens A, Haase J, Vicci L, Taylor 2nd R, Bloom K . Cohesin, condensin, and the intramolecular centromere loop together generate the mitotic chromatin spring. J Cell Biol. 2011; 193(7):1167-80. PMC: 3216333. DOI: 10.1083/jcb.201103138. View

Dernburg A, Sedat J, Hawley R . Direct evidence of a role for heterochromatin in meiotic chromosome segregation. Cell. 1996; 86(1):135-46. DOI: 10.1016/s0092-8674(00)80084-7. View

Tsubouchi T, Roeder G . A synaptonemal complex protein promotes homology-independent centromere coupling. Science. 2005; 308(5723):870-3. DOI: 10.1126/science.1108283. View

Koszul R, Kim K, Prentiss M, Kleckner N, Kameoka S . Meiotic chromosomes move by linkage to dynamic actin cables with transduction of force through the nuclear envelope. Cell. 2008; 133(7):1188-201. PMC: 2601696. DOI: 10.1016/j.cell.2008.04.050. View

Molnar M, Bahler J, Sipiczki M, Kohli J . The rec8 gene of Schizosaccharomyces pombe is involved in linear element formation, chromosome pairing and sister-chromatid cohesion during meiosis. Genetics. 1995; 141(1):61-73. PMC: 1206740. DOI: 10.1093/genetics/141.1.61. View

Obeso D, Dawson D . Temporal characterization of homology-independent centromere coupling in meiotic prophase. PLoS One. 2010; 5(4):e10336. PMC: 2859069. DOI: 10.1371/journal.pone.0010336. View

10.

Davis L, Smith G . The meiotic bouquet promotes homolog interactions and restricts ectopic recombination in Schizosaccharomyces pombe. Genetics. 2006; 174(1):167-77. PMC: 1569800. DOI: 10.1534/genetics.106.059733. View

11.

Lin W, Jin H, Liu X, Hampton K, Yu H . Scc2 regulates gene expression by recruiting cohesin to the chromosome as a transcriptional activator during yeast meiosis. Mol Biol Cell. 2011; 22(12):1985-96. PMC: 3113765. DOI: 10.1091/mbc.E10-06-0545. View

12.

Starr D, Fridolfsson H . Interactions between nuclei and the cytoskeleton are mediated by SUN-KASH nuclear-envelope bridges. Annu Rev Cell Dev Biol. 2010; 26:421-44. PMC: 4053175. DOI: 10.1146/annurev-cellbio-100109-104037. View

13.

Burgess S, Kleckner N, Weiner B . Somatic pairing of homologs in budding yeast: existence and modulation. Genes Dev. 1999; 13(12):1627-41. PMC: 316803. DOI: 10.1101/gad.13.12.1627. View

14.

Wach A, Brachat A, Pohlmann R, Philippsen P . New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994; 10(13):1793-808. DOI: 10.1002/yea.320101310. View

15.

Panizza S, Mendoza M, Berlinger M, Huang L, Nicolas A, Shirahige K . Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination. Cell. 2011; 146(3):372-83. DOI: 10.1016/j.cell.2011.07.003. View

16.

Schober H, Ferreira H, Kalck V, Gehlen L, Gasser S . Yeast telomerase and the SUN domain protein Mps3 anchor telomeres and repress subtelomeric recombination. Genes Dev. 2009; 23(8):928-38. PMC: 2675861. DOI: 10.1101/gad.1787509. View

17.

Baudat F, Manova K, Yuen J, Jasin M, Keeney S . Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Mol Cell. 2000; 6(5):989-98. DOI: 10.1016/s1097-2765(00)00098-8. View

18.

Zickler D, Kleckner N . Meiotic chromosomes: integrating structure and function. Annu Rev Genet. 2000; 33:603-754. DOI: 10.1146/annurev.genet.33.1.603. View

19.

Bloom K, Joglekar A . Towards building a chromosome segregation machine. Nature. 2010; 463(7280):446-56. PMC: 2879044. DOI: 10.1038/nature08912. View

20.

Oh S, Lao J, Taylor A, Smith G, Hunter N . RecQ helicase, Sgs1, and XPF family endonuclease, Mus81-Mms4, resolve aberrant joint molecules during meiotic recombination. Mol Cell. 2008; 31(3):324-36. PMC: 2587322. DOI: 10.1016/j.molcel.2008.07.006. View