Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis

Huanyu Qiao, Jefferson K. Chen, April Reynolds, Christer Höög, Michael Paddy, Neil Hunter

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC-dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC-dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post-SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1-/- implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function.

Original languageEnglish (US)
Article numbere1002790
JournalPLoS Genetics
Volume8
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Synaptonemal Complex
synaptonemal complex
Centromere
Homologous Recombination
homologous recombination
Meiosis
centromeres
meiosis
recombination
chromosome
yeast
microscopy
Chromosome Pairing
Meiotic Prophase I
chiasmata
mammal
fruit
prophase
DNA
Saccharomycetales

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis. / Qiao, Huanyu; Chen, Jefferson K.; Reynolds, April; Höög, Christer; Paddy, Michael; Hunter, Neil.

In: PLoS Genetics, Vol. 8, No. 6, e1002790, 06.2012.

Research output: Contribution to journalArticle

Qiao, Huanyu ; Chen, Jefferson K. ; Reynolds, April ; Höög, Christer ; Paddy, Michael ; Hunter, Neil. / Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis. In: PLoS Genetics. 2012 ; Vol. 8, No. 6.
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