Meiotic crossover number and distribution are regulated by a dosage compensation protein that resembles a condensin subunit.
Biological processes that function chromosome-wide are not well understood. Here, we show that the Caenorhabditis elegans protein DPY-28 controls two such processes, X-chromosome dosage compensation in somatic cells and meiotic crossover number and distribution in germ cells. DPY-28 resembles a subunit of condensin, a conserved complex required for chromosome compaction and segregation. In the soma, DPY-28 associates with the dosage compensation complex on hermaphrodite X chromosomes to repress transcript levels. In the germline, DPY-28 restricts crossovers. In many organisms, one crossover decreases the likelihood of another crossover nearby, an enigmatic process called crossover interference. In C. elegans, interference is complete: Only one crossover occurs per homolog pair. dpy-28 mutations increase crossovers, disrupt crossover interference, and alter crossover distribution. Early recombination intermediates (RAD-51 foci) increase concomitantly, suggesting that DPY-28 acts to limit double-strand breaks (DSBs). Reinforcing this view, dpy-28 mutations partially restore DSBs in mutants lacking HIM-17, a chromatin-associated protein required for DSB formation. Our work further links dosage compensation to condensin and establishes a new role for condensin components in regulating crossover number and distribution. We propose that both processes utilize a related mechanism involving changes in higher-order chromosome structure to achieve chromosome-wide effects.
Tsai
Chun J
CJ
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 97420, USA.
Mets
David G
DG
Albrecht
Michael R
MR
Nix
Paola
P
Chan
Annette
A
Meyer
Barbara J
BJ
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D019457:Chromosome Breakage; D003434:Crossing Over, Genetic; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D012734:Disorders of Sex Development; D004303:Dosage Compensation, Genetic; D044127:Epigenesis, Genetic; D008540:Meiosis; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics; D009154:Mutation; D014960:X Chromosome
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C491265:HIM-17 protein, C elegans; D046912:Multiprotein Complexes; C079666:Sdc-3 protein, C elegans; C108312:condensin complexes; D000251:Adenosine Triphosphatases