Fig. 7.

Model for how HIM-17 regulates DSB/CO distribution and late prophase I chromosome remodeling. HIM-17 acts in early prophase I by regulating DSB levels and DSB-dependent RAD-51 foci/CO distribution. In wild type, an excess number of DSBs are made, and a higher number of DSB-dependent RAD-51 foci is observed on the arms compared to the center region of the chromosomes in C. elegans. One DSB on the arm regions of the chromosomes is processed into a CO. This off-center CO position results in the production of an asymmetric bivalent with long (L) and short (S) arms. During late prophase I, recruitment of GSP-1/2 by LAB-1 and phosphorylation of GSP-1 at the S2 site, which requires HIM-17 function, prevents phosphorylation of H3T3 on the long arm, thereby preventing AIR-2 loading on the long arm. In contrast, in him-17 mutants, a reduced number of DSBs are made, and their distribution is altered such that now higher levels of DSB-dependent RAD-51 foci are detected at the center of the chromosomes. An increase in the levels of COs on the center of the chromosomes is observed, which potentially contributes to the short arm identity defect. In addition, expression, localization, and probably phosphorylation of GSP-1/2 is impaired, leading to phosphorylation of H3pT3 on the long arms even when LAB-1 is properly localized to the long arm of the bivalents. Therefore, HIM-17 functions at early and late prophase I are required to impede altered CO position and impaired GSP-1/2 activity to promote normal chromosome remodeling and subsequent regulated stepwise loss of SCC, leading to accurate chromosome segregation.