Genetic analysis of Caenorhabditis elegans Haspin-like genes shows that hasp-1 plays multiple roles in the germline

Abstract

Haspin is a histone kinase that promotes error-free chromosome segregation by recruiting the Chromosomal Passenger Complex (CPC) to mitotic and meiotic chromosomes. Haspin remains less well studied than other M-phase kinases and the models explaining Haspin function have been developed primarily in mitotic cells. Here, we generate strains containing new conditional or nonsense mutations in the C. elegans Haspin homologs hasp-1 and hasp-2 and characterize their phenotypes. We show that hasp-1 is responsible for all predicted functions of Haspin and that loss of function of hasp-1 using classical and conditional alleles produces defects in germline stem cell proliferation, spermatogenesis, and confirms its role in oocyte meiosis. Genetic analysis suggests hasp-1 acts downstream of the Polo-like kinase plk-2 and shows synthetic interactions between hasp-1 and two genes expected to promote recruitment of the CPC by a parallel pathway that depends on the kinase Bub1. This work adds to the growing understanding of Haspin function by characterizing a variety of roles in an intact animal.

Cohesin is required for meiotic spindle assembly independent of its role in cohesion in C. elegans

“…Timelapse imaging of mNeonGreen::tubulin in bir-1(E69A, D70A) mutants revealed apolar metaphase spindles that shrank without chromosome separation during both meiosis I and meiosis II (Fig 6A) ). Because a hasp-1(null) mutant is completely sterile [46], the low hatch rate suggested that the low frequency of bipolar spindles in HASP-1-depleted worms was due to incomplete depletion by the degron. Because haspin is recruited to chromosomes by cohesin-associated PDS5 [32], these results indicated that the subclass of Aurora B that is recruited to chromosomes by cohesin and haspin-dependent phosphorylation of histone H3 is required for bipolar spindle assembly and that cohesin-independent and haspin-independent Aurora B on chromosome lobes and anaphase microtubules are not sufficient to drive bipolar spindle assembly.…”