PT - JOURNAL ARTICLE AU - Meneely, Philip M. AU - McGovern, Olivia L. AU - Heinis, Frazer I. AU - Yanowitz, Judith L. TI - Crossover Distribution and Frequency Are Regulated by <em>him-5</em> in <em>Caenorhabditis elegans</em> AID - 10.1534/genetics.111.137463 DP - 2012 Apr 01 TA - Genetics PG - 1251--1266 VI - 190 IP - 4 4099 - http://www.genetics.org/content/190/4/1251.short 4100 - http://www.genetics.org/content/190/4/1251.full SO - Genetics2012 Apr 01; 190 AB - Mutations in the him-5 gene in Caenorhabditis elegans strongly reduce the frequency of crossovers on the X chromosome, with lesser effects on the autosomes. him-5 mutants also show a change in crossover distribution on both the X and autosomes. These phenotypes are accompanied by a delayed entry into pachytene and premature desynapsis of the X chromosome. The nondisjunction, progression defects and desynapsis can be rescued by an exogenous source of double strand breaks (DSBs), indicating that the role of HIM-5 is to promote the formation of meiotic DSBs. Molecular cloning of the gene shows that the inferred HIM-5 product is a highly basic protein of 252 amino acids with no clear orthologs in other species, including other Caenorhabditis species. Although him-5 mutants are defective in segregation of the X chromosome, HIM-5 protein localizes preferentially to the autosomes. The mutant phenotypes and localization of him-5 are similar but not identical to the results seen with xnd-1, although unlike xnd-1, him-5 has no apparent effect on the acetylation of histone H2A on lysine 5 (H2AacK5). The localization of HIM-5 to the autosomes depends on the activities of both xnd-1 and him-17 allowing us to begin to establish pathways for the control of crossover distribution and frequency.