The Chromosome Axis Mediates Feedback Control of CHK-2 to Ensure Crossover Formation in C. elegans

Dev Cell. 2015 Oct 26;35(2):247-61. doi: 10.1016/j.devcel.2015.09.021.

Abstract

CHK-2 kinase is a master regulator of meiosis in C. elegans. Its activity is required for homolog pairing and synapsis and for double-strand break formation, but how it drives and coordinates these pathways to ensure crossover formation remains unknown. Here we show that CHK-2 promotes pairing and synapsis by phosphorylating a family of zinc finger proteins that bind to specialized regions on each chromosome known as pairing centers, priming their recruitment of the Polo-like kinase PLK-2. This knowledge enabled the development of a phospho-specific antibody as a tool to monitor CHK-2 activity. When either synapsis or crossover formation is impaired, CHK-2 activity is prolonged, and meiotic progression is delayed. We show that this common feedback circuit is mediated by interactions among a network of HORMA domain proteins within the chromosome axis and generates a graded signal. These findings reveal conserved regulatory mechanisms that ensure faithful meiotic chromosome segregation in diverse species.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Checkpoint Kinase 2 / genetics*
  • Checkpoint Kinase 2 / metabolism
  • Chromosome Pairing / genetics
  • Chromosome Segregation / genetics*
  • Chromosomes / genetics
  • Crossing Over, Genetic
  • DNA Breaks, Double-Stranded
  • Meiosis / genetics*
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Checkpoint Kinase 2
  • CHK-2 protein, C elegans
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 2, C elegans