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

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

Author information

1
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3220, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA.
2
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3220, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA; Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, Berkeley, CA 94720, USA. Electronic address: afdernburg@berkeley.edu.

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.

PMID:
26506311
PMCID:
PMC4624198
DOI:
10.1016/j.devcel.2015.09.021
[Indexed for MEDLINE]
Free PMC Article

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