Caenorhabditis elegans EVL-14/PDS-5 and SCC-3 Are Essential for Sister Chromatid Cohesion in Meiosis and Mitosis

Abstract

Sister chromatid cohesion is fundamental for the faithful transmission of chromosomes during both meiosis and mitosis. Proteins involved in this process are highly conserved from yeasts to humans. In screenings for sterile animals with abnormal vulval morphology, mutations in the Caenorhabditis elegans evl-14 and scc-3 genes were isolated. Defects in cell divisions were observed in germ line as well as in vulval and somatic gonad lineages. Through positional cloning of these genes, we have shown that EVL-14 and SCC-3 are likely the only C. elegans homologs of the yeast sister chromatid cohesion proteins Pds5 and Scc3, respectively. Both evl-14 and scc-3 mutants displayed defects in the meiotic germ line. In evl-14 mutants, synaptonemal complexes (SCs) were detectable but more than the usual six DAPI (4,6-diamidino-2-phenylindole)-positive structures were seen at diakinesis, suggesting that EVL-14/PDS-5 is important for the maintenance of sister chromatid cohesion in late prophase. In scc-3 mutant animals, normal SCs were not visible and ϳ24 DAPI-positive structures were seen at diakinesis, indicating that SCC-3 is necessary for sister chromatid cohesion. Immunostaining revealed that localization of REC-8, a homolog of the yeast meiotic cohesin subunit Rec8, to the chromosomes depends on the presence of SCC-3 but not that of EVL-14/PDS-5. scc-3 RNA interference (RNAi)-treated embryos were 100% lethal and displayed defects in cell divisions. evl-14 RNAi caused a range of phenotypes. These results indicate that EVL-14/PDS-5 and SCC-3 have functions in both mitosis and meiosis.In eukaryotes, the faithful transmission of chromosomes during both meiosis and mitosis is critical for species propagation and the survival of individual organisms. Sister chromatid cohesion is fundamental to this process. In mitosis and meiosis II, sister chromatid cohesion ensures proper binding of sister kinetochores to spindle pole microtubules. In meiosis I, it is also required to arrange kinetochores associated with homologous chromosomes to face the appropriate spindle poles. Sister chromatid cohesion is established during the S phase and persists until the onset of anaphase (for reviews, see references 27, 35, and 47).A multiprotein complex called cohesin is a major effector of sister chromatid cohesion. The complex consists of at least four conserved subunits, homologs of which have been identified in all major phyla. In Saccharomyces cerevisiae they are Scc1/ Mcd1, Scc3, Smc1, and Smc3, which colocalize to chromatin in an interdependent manner (18,31,46). Scc1 is replaced in meiosis by its paralogue Rec8 (7, 25). In Caenorhabditis elegans there are four Scc1 homologs of which one, REC-8, is the likely worm ortholog of yeast Rec8 (34). Scc3 has multiple homologs in other species as well. Fission yeast contains two homologs of Scc3: Psc3 and the predicted meiosis-specific member Rec11 (13, 26,45). Three Scc3 homologs, SA1 to SA3 (stromal antigen 1 to 3) (of which one, SA3, joins the meiotic cohesin complex) (8, 28,36,42), have been fo...

The cohesin-interacting protein, precocious dissociation of sisters 5A/sister chromatid cohesion protein 112, is up-regulated in human astrocytic tumors

“…Pds5A is a cohesin complex-interacting protein, which is involved in the establishment, maintenance and dissolution of sister chromatid cohesion (27)(28)(29)(30)34,35). Although details about its function remain unresolved, it could also play a role in tumorigenesis (25,26).…”

“…In fission yeast and vertebrate cells, separase plays a less important role in sister chromatid separation and it is thought that other mechanisms could regulate chromatid segregation in these cell types (30). It has been shown that Pds5 could be involved in the establishment, maintenance and dissolution of cohesion in both yeasts and humans (27)(28)(29)(30)34,35). It could also be implicated in embryonic development (36).…”

“…It is highly conserved from yeast to man (Table I) and interacts with the cohesin protein complex, although it is not a cohesin subunit itself (23,24,(27)(28)(29)(30). Cohesin forms a ring-like structure and holds sister chromatids together until spindle fibers attach to the kinetochores (9,(31)(32)(33).…”

Proteomic analysis of long term salt responsive proteins in the halophyte Suaeda maritima

“…The cohesion complex proteins present in the nuclear matrix are involved in chromosome organization and the establishment of chromosome boundaries. The cohesion protein SCC3 was first identified as a member of the yeast mitotic cohesin complex (Toth et al, 1999) and was subsequently identified in Caenorhabditis elegans and Arabidopsis (Pasierbek et al, 2003;Wang et al, 2003).This SCC3 protein (spot no.4) was identified in our study shows 12% amino acid sequence homology with Arabidopsis. In Arabidopsis, SCC3 protein expressed in roots, mature leaves and is mainly involved in both meiotic and mitotic divisions.…”

Meiotic recombination in Caenorhabditis elegans

“…In yeast only Scc1 is replaced by meiosis-specific Rec8 (Klein et al 1999, Watanabe & Nurse 1999, whereas in mammalian meiosis two additional replacements occur: Smc1 by Smc1b, and STAG3 for SA1/SA2 (Prieto et al 2001, Revenkova et al 2001. While single candidates where found for SCC-3 (Wang et al 2003) and the two subunits belonging to the structural maintenance of chromosomes (SMC) family , Chan et al 2003, SMC-1 (or HIM-1) and SMC-3, REC-8 is one of the four Rad21/Scc1/Rec8 homologs present in C. elegans genome (Pasierbek et al 2001). REC-8 localizes at chromosomal axes throughout meiosis I, and depletion causes embryonic lethality, a strong Him phenotype and cytological defects associated with defective synapsis and premature separation of sister chromatids prior to the first meiotic division.…”