Phosphorylation of the synaptonemal complex protein SYP-1 promotes meiotic chromosome segregation

Abstract

Chromosomes that have undergone crossing-over in meiotic prophase must maintain sister chromatid cohesion somewhere along their length between the first and second meiotic divisions. While many eukaryotes use the centromere as a site to maintain cohesion, the holocentric organism C. elegans instead creates two chromosome domains of unequal length termed the short arm and long arm, which become the first and second site of cohesion loss at meiosis I and II. The mechanisms that confer distinct functions to the short and long arm domains remain poorly understood. Here, we show that phosphorylation of the synaptonemal complex protein SYP-1 is required to create these domains. Once crossovers are made, phosphorylated SYP-1 and PLK-2 become cooperatively confined to short arms and guide phosphorylated histone H3 and the chromosomal passenger complex to the site of meiosis I cohesion loss. Our results show that PLK-2 and phosphorylated SYP-1 ensure creation of the short arm subdomain, promoting disjunction of chromosomes in meiosis I.

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase inC. elegans

“…To understand regulation of meiotic proteins by post-translational modification, we previously carried out mass spectrometry to identify phosphorylated proteins in C. elegans adult hermaphrodites [16] . In two independent experiments, we found that the chromosome axis protein HIM-3 is phosphorylated at its C-terminus.…”

“…As oocyte precursor cells progress into late pachytene, designate crossovers, and begin to differentiate long and short arms, HIM-3phos antibody staining becomes enriched on only a small, terminal part of the SC, in contrast to panHIM-3 staining which remains on the full length of the SC, suggesting that phosphorylated HIM-3 becomes enriched on the short arm ( Figure 2B ). Simultaneous staining with the short arm marker SYP-1phos antibody [16] as well as the crossover designation marker COSA-1 [32] revealed that phosphorylated HIM-3 becomes enriched at short arms once crossovers are designated ( Figure 2C ). Although Ser282 is in an ATM/ATR kinase consensus site (SQ), we found that phosphorylation of HIM-3 Ser282 does not depend on these DNA damage-responsive kinases ( Supplemental Figure 1C ).…”

“…The E3 ligases ZHP-1 and ZHP-2, that act with partners ZHP-3 and ZHP-4 to ensure the formation of a single crossover per chromosome, localize to short arms and are required for asymmetric SC disassembly [15] . In addition, phosphoregulation of the SC transverse and central elements, SYP-1 and SYP-2, is known to promote establishment of short and long arms [16,17] . MAP kinase-mediated phosphorylation of SYP-2 and subsequent inactivation of MAPK upon crossover designation triggers disassembly of SC central element proteins from the long arm [17] .…”

“…Phosphorylation at the Polo Box Domain (PBD) binding motif of SYP-1 at Thr452 promotes the cascade of short and long arm establishment by recruiting PLK-2 to the SC. Phosphorylated SYP-1 and PLK-2 are mutually dependent for their colocalization on short arms upon crossover designation, and a non-phosphorylatable syp-1 mutation leads to loss of asymmetry and failure in meiosis I segregation [16] . Once short/long asymmetry is established, the chromosome passenger complex (CPC) containing INCENP ICP-1 and Aurora B AIR-2 is recruited to the short arm by Haspin kinase phosphorylation of histone H3Thr3 [16,[18][19][20] .…”

“…Phosphorylated SYP-1 and PLK-2 are mutually dependent for their colocalization on short arms upon crossover designation, and a non-phosphorylatable syp-1 mutation leads to loss of asymmetry and failure in meiosis I segregation [16] . Once short/long asymmetry is established, the chromosome passenger complex (CPC) containing INCENP ICP-1 and Aurora B AIR-2 is recruited to the short arm by Haspin kinase phosphorylation of histone H3Thr3 [16,[18][19][20] . H3Thr3 in turn is dephosphorylated on the long arm by HTP-1/LAB-1-based recruitment of phosphatase PP1 [18,21] .…”