The Chromosome Axis Mediates Feedback Control of CHK-2 to Ensure Crossover Formation in C. elegans.
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.
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.
Yumi
Y
Kim
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.
Nora
N
Kostow
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.
Abby F
AF
Dernburg
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000235:genetics* / Q000378:metabolism; D023902:Chromosome Pairing / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D008540:Meiosis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D000097868:Polo-like Kinases
D029742:Caenorhabditis elegans Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C444421:CHK-2 protein, C elegans; C569597:polo-like kinase 2, C elegans; D000097868:Polo-like Kinases