%0 Generic %A Nguyen, Hanh %A Labella, Sara %A Silva, Nicola %A Jantsch, Verena %A Zetka, Monique %D 2018 %T C. elegans ZHP-4 is required at multiple distinct steps in the formation of crossovers and their transition to segregation competent chiasmata %U https://plos.figshare.com/articles/dataset/_i_C_i_i_elegans_i_ZHP-4_is_required_at_multiple_distinct_steps_in_the_formation_of_crossovers_and_their_transition_to_segregation_competent_chiasmata/7279244 %R 10.1371/journal.pgen.1007776 %2 https://plos.figshare.com/ndownloader/files/13443128 %2 https://plos.figshare.com/ndownloader/files/13443131 %2 https://plos.figshare.com/ndownloader/files/13443134 %2 https://plos.figshare.com/ndownloader/files/13443137 %2 https://plos.figshare.com/ndownloader/files/13443140 %2 https://plos.figshare.com/ndownloader/files/13443143 %2 https://plos.figshare.com/ndownloader/files/13443146 %2 https://plos.figshare.com/ndownloader/files/13443149 %K elegans protein ZHP -4 %K JM %K zhp -4 mutants %K RNF 212-like C %K paralog ZHP -3 %K ZHP -4 %K formation %K transition %K elegans ZHP -4 %K chiasmata %K COSA %K RMH %K CO %K segregation %K pro-crossover factors %K SC %K MSH %K DNA %K hypomorphic mutants exhibit %K RING domain mutants %K NCO %K ZHP -4 function %K ZHP -4 acts %X

Correct segregation of meiotic chromosomes depends on DNA crossovers (COs) between homologs that culminate into visible physical linkages called chiasmata. COs emerge from a larger population of joint molecules (JM), the remainder of which are repaired as noncrossovers (NCOs) to restore genomic integrity. We present evidence that the RNF212-like C. elegans protein ZHP-4 cooperates with its paralog ZHP-3 to enforce crossover formation at distinct steps during meiotic prophase: in the formation of early JMs and in transition of late CO intermediates into chiasmata. ZHP-3/4 localize to the synaptonemal complex (SC) co-dependently followed by their restriction to sites of designated COs. RING domain mutants revealed a critical function for ZHP-4 in localization of both proteins to the SC and for CO formation. While recombination initiates in zhp-4 mutants, they fail to appropriately acquire pro-crossover factors at abundant early JMs, indicating a function for ZHP-4 in an early step of the CO/NCO decision. At late pachytene stages, hypomorphic mutants exhibit significant levels of crossing over that are accompanied by defects in localization of pro-crossover RMH-1, MSH-5 and COSA-1 to designated crossover sites, and by the appearance of bivalents defective in chromosome remodelling required for segregation. These results reveal a ZHP-4 function at designated CO sites where it is required to stabilize pro-crossover factors at the late crossover intermediate, which in turn are required for the transition to a chiasma that is required for bivalent remodelling. Our study reveals an essential requirement for ZHP-4 in negotiating both the formation of COs and their ability to transition to structures capable of directing accurate chromosome segregation. We propose that ZHP-4 acts in concert with ZHP-3 to propel interhomolog JMs along the crossover pathway by stabilizing pro-CO factors that associate with early and late intermediates, thereby protecting designated crossovers as they transition into the chiasmata required for disjunction.

%I PLOS Genetics