| RRC ID |
59389
|
| 著者 |
Nguyen H, Labella S, Silva N, Jantsch V, Zetka M.
|
| タイトル |
C. elegans ZHP-4 is required at multiple distinct steps in the formation of crossovers and their transition to segregation competent chiasmata.
|
| ジャーナル |
PLoS Genet
|
| Abstract |
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.
|
| 巻・号 |
14(10)
|
| ページ |
e1007776
|
| 公開日 |
2018-10-1
|
| DOI |
10.1371/journal.pgen.1007776
|
| PII |
PGENETICS-D-18-01164
|
| PMID |
30379819
|
| PMC |
PMC6239344
|
| MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Chromosomal Proteins, Non-Histone / genetics
Chromosome Segregation / genetics*
Chromosome Structures / metabolism
Crossing Over, Genetic / genetics*
Crossing Over, Genetic / physiology
DNA-Binding Proteins / genetics
Meiosis
Synaptonemal Complex / metabolism
|
| IF |
5.224
|
| 引用数 |
5
|
| リソース情報 |
| 線虫 |
tm1937
tm3298 |
