Chromosome segregation in meiosis requires the proper number and position of crossovers. Yet chromosomes show characteristic distributions and numbers of crossover events suggesting that chromosome-specific factors are shaping the crossover landscape. A growing body of evidence implicates chromatin structure as a major determinant of crossover distribution. Nevertheless, the genes involved in this process have remained largely unknown. Many meiotic mutants, known as precondition mutants, alter the crossover landscape. It is likely that analysis of these mutants will reveal the underlying state of chromatin along the chromosomes. We have been analyzing the C. elegans precondition mutant
him-5.
him-5 was identified in Hodgkin''s original HIM screen and was shown to have strong specificity for the X chromosome. We have analyzed his alleles
e1467 and
e1490, as well as a null allele,
ok1896. All three mutants cause an increase in male self-progeny ranging from 20-40% caused by a failure of recombination on the X chromosomes. In addition, all three alleles show a slight increase in autosomal nondisjunction, with age-related changes in the spectrum of severity. We show that
him-5 is defective in making the double strand breaks that initiate recombination. We can completely rescue the X and autosomal nondisjunction phenotypes by creating breaks with ionizing radiation. In the mutant, chromosomes are completely paired and synapsed, but they prematurely disassemble the synaptonemal complex on the X chromosome, a phenotype that is also rescued by irradiation. These results are striking because it was previously thought that chromosome-specific meiotic functions were confined to homologue recognition and pairing. Together with our work on
xnd-1 (which has a similar phenotype), we have defined a novel step at which chromosome-specific identities are essential for proper disjunction.
him-5 corresponds to D1086.4 and encodes a protein with no known homologues outside of C. elegans. Two-hybrid analysis suggests that HIM-5 acts in a protein complex but the precise function of this complex is unknown. HIM-5 and XND-1 act independently of one another suggesting that further analysis of HIM-5 will elucidate novel aspects of chromosome-specific crossover control.