A novel mammalian HORMA domain-containing protein, HORMAD1, preferentially associates with unsynapsed meiotic chromosomes

Exp Cell Res. 2010 Jan 15;316(2):158-71. doi: 10.1016/j.yexcr.2009.08.007. Epub 2009 Aug 15.

Abstract

HORMA domain-containing proteins regulate interactions between homologous chromosomes (homologs) during meiosis in a wide range of eukaryotes. We have identified a mouse HORMA domain-containing protein, HORMAD1, and biochemically and cytologically shown it to be associated with the meiotic chromosome axis. HORMAD1 first accumulates on the chromosomes during the leptotene to zygotene stages of meiotic prophase I. As germ cells progress into the pachytene stage, HORMAD1 disappears from the synapsed chromosomal regions. However, once the chromosomes desynapse during the diplotene stage, HORMAD1 again accumulates on the chromosome axis of the desynapsed homologs. HORMAD1 thus preferentially localizes to unsynapsed or desynapsed chromosomal regions during the prophase I stage of meiosis. Analysis of mutant strains lacking different components of the synaptonemal complex (SC) revealed that establishment of the SC is required for the displacement of HORMAD1 from the chromosome axis. Our results therefore strongly suggest that also mammalian cells use a HORMA domain-containing protein as part of a surveillance system that monitors synapsis or other interactions between homologs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA1 Protein / metabolism
  • COS Cells
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Pairing / physiology*
  • Chromosomes, Mammalian / metabolism*
  • DNA-Binding Proteins
  • Embryo, Mammalian / metabolism
  • Female
  • Histones / metabolism
  • Male
  • Meiosis / physiology*
  • Meiotic Prophase I / physiology
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oocytes / metabolism
  • Pachytene Stage / physiology
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Spermatocytes / metabolism
  • Synaptonemal Complex / metabolism
  • Testis / metabolism
  • Transfection

Substances

  • BRCA1 Protein
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • H2AX protein, mouse
  • Histones
  • Nohma protein, mouse
  • Nuclear Proteins
  • Protein Isoforms
  • Stag3 protein, mouse
  • Sycp1 protein, mouse
  • Sycp3 protein, mouse
  • TEX12 protein, mouse
  • cohesins