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cell division cycle 20 OKDB#: 3093
 Symbols: CDC20 Species: human
 Synonyms: CDC20A, p55CDC, bA276H19.3  Locus: 1p34.2 in Homo sapiens


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General Comment NCBI Summary: CDC20 appears to act as a regulatory protein interacting with several other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes, nuclear movement prior to anaphase and chromosome separation. [provided by RefSeq, Jul 2008]
General function Cell cycle regulation
Comment
Cellular localization Cytoplasmic
Comment
Ovarian function Oogenesis, Oocyte maturation, Early embryo development , First polar body extrusion
Comment CDC20 downregulation impairs spindle morphology and causes reduced first polar body emission during bovine oocyte maturation. Yang WL 2013 et al. The cell division cycle protein 20 (CDC20) is an essential regulator of cell division, encoded by the CDC20 gene. However, the role of CDC20 in bovine oocyte maturation is unknown. In this study, CDC20 morpholino antisense oligonucleotides (MOs) were microinjected into the cytoplasm of bovine oocytes to block the translation of CDC20 mRNA. CDC20 downregulation significantly reduced the rate of first polar body emission (PB1). Further analysis indicated that oocytes treated with CDC20 MO arrested before or at meiotic stage I with abnormal spindles. To further confirm the functions of CDC20 during oocyte meiotic division, CDC20 MOs were microinjected into oocytes together with a supplementary PB1. The results showed that newly synthesized CDC20 was not necessary at the meiosis II-to-anaphase II transition. Our data suggest that CDC20 is required for spindle assembly, chromosomal segregation, and PB1 extrusion during bovine oocyte maturation. ///////////////////////// Cdc20 is Required for the Anaphase Onset of the First Meiosis but not the Second Meiosis in Mouse Oocytes. Yin S et al. In meiosis, two successive divisions occur with only one round of DNA replication, thereby producing haploid gametes. Vertebrate eggs arrest at metaphase of the second meiotic division caused by cytostatic factor (CSF)(1) until fertilization. Errors in this process result in aneuploidy, and developmental, physiological as well as mental disturbances that are manifested in genetic disorders. Mitotic cells have developed a high-fidelity surveillance mechanism termed the spindle checkpoint to prevent chromosome missegregation by delaying onset of anaphase until all sister chromatids are correctly attached to the spindle. Studies in several model systems have proposed that the downstream target of the spindle checkpoint is Cdc20, an activator of anaphase promoting complex/cyclosome (APC/C) which is an 11-subunit complex containing ubiquitin ligase activity.(2) The metaphase-to-anaphase transition is induced by APC/C. The mitotic spindle checkpoint transmits inhibitory signals to APC/CCdc20, stabilizing securin (Pds1) and cyclin B, and thus prevents the metaphase-anaphase transition until all chromosomes have established a bipolar attachment to the spindle.(3).
Expression regulated by
Comment
Ovarian localization Oocyte
Comment The human cumulus-oocyte complex gene-expression profile. Assou S et al. BACKGROUND: The understanding of the mechanisms regulating human oocyte maturation is still rudimentary. We have identified transcripts differentially expressed between immature and mature oocytes and cumulus cells.
Follicle stages
Comment Functions of FZR1 and CDC20, Activators of the Anaphase-Promoting Complex, During Meiotic Maturation of Swine Oocytes. Yamamuro T et al. CDC20 and FZR1 are activators of the anaphase-promoting complex (APC), which ubiquitinates M-phase regulating proteins, such as cyclin B and securin, and induces their degradation. In the present study, porcine CDC20 and FZR1 were cloned by reverse transcriptase-polymerase chain reaction and their functions in the meiotic maturation of porcine oocytes were analyzed. FZR1 was readily detected in porcine immature oocytes by immunoblotting but its levels decreased substantially during maturation. In contrast CDC20 levels rose during oocyte maturation and were highest by the second meiotic metaphase (M2). The inhibition of CDC20 expression by the injection of CDC20 antisense RNA induced the meiotic arrest at the first meiotic metaphase (M1) and the accumulation of a large amount of cyclin B. On the other hand, the inhibition of FZR1 expression accelerated the cyclin B accumulation and the start of GVBD, but did not affect the exit from M1. Conversely, the overexpression of FZR1 by the injection of FZR1 mRNA suppressed the cyclin B accumulation and retarded GVBD. Surprisingly, the injection of CDC20 mRNA into the immature oocytes could not increase CDC20 expression, but increased cyclin B accumulation and accelerated the meiotic progression. As CDC20 is a substrate of APC (FZR1), CDC20 might have competed with cyclin B and inhibited the FZR1 function. These results suggest that porcine FZR1 and CDC20 work on the maintenance of meiotic arrest at the first meiotic prophase and on the exit from M1, respectively, and that their functional phases are strictly distinguished during porcine oocyte maturation.
Phenotypes POF (premature ovarian failure)
Mutations 5 mutations

Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: Cdc20 is critical for meiosis I and fertility of female mice. Jin F et al. Chromosome missegregation in germ cells is an important cause of unexplained infertility, miscarriages, and congenital birth defects in humans. However, the molecular defects that lead to production of aneuploid gametes are largely unknown. Cdc20, the activating subunit of the anaphase-promoting complex/cyclosome (APC/C), initiates sister-chromatid separation by ordering the destruction of two key anaphase inhibitors, cyclin B1 and securin, at the transition from metaphase to anaphase. The physiological significance and full repertoire of functions of mammalian Cdc20 are unclear at present, mainly because of the essential nature of this protein in cell cycle progression. To bypass this problem we generated hypomorphic mice that express low amounts of Cdc20. These mice are healthy and have a normal lifespan, but females produce either no or very few offspring, despite normal folliculogenesis and fertilization rates. When mated with wild-type males, hypomorphic females yield nearly normal numbers of fertilized eggs, but as these embryos develop, they become malformed and rarely reach the blastocyst stage. In exploring the underlying mechanism, we uncover that the vast majority of these embryos have abnormal chromosome numbers, primarily due to chromosome lagging and chromosome misalignment during meiosis I in the oocyte. Furthermore, cyclin B1, cyclin A2, and securin are inefficiently degraded in metaphase I; and anaphase I onset is markedly delayed. These results demonstrate that the physiologically effective threshold level of Cdc20 is high for female meiosis I and identify Cdc20 hypomorphism as a mechanism for chromosome missegregation and formation of aneuploid gametes.

Species: human
Mutation name:
type: naturally occurring
fertility: infertile - ovarian defect
Comment: Biallelic mutations in CDC20 cause female infertility characterized by abnormalities in oocyte maturation and early embryonic development. Zhao L et al. (2020)//////////////////

Species: human
Mutation name:
type: naturally occurring
fertility: infertile - ovarian defect
Comment: Novel Mutations in CDC20 Are Associated with Female Infertility Due to Oocyte Maturation Abnormality and Early Embryonic Arrest. Huang L et al. (2021) The cell division cycle 20 (CDC20) protein is a co-activator of anaphase-promoting complex/cyclosome (APC/C), required for mitotic exit and also meiotic exit, containing seven WD40 repeats in the C-terminus responsible for protein-protein interactions. Recently, a previous study has shown that biallelic mutations in CDC20 are causative for female infertility with abnormalities in oocyte maturation and embryonic development. This study is to further identify new mutations of CDC20 and the prevalence of variants in our cohort. A cohort of 50 primary infertile females with oocyte maturation abnormality and early embryonic arrest were recruited. Genomic DNA was isolated from peripheral blood samples. Mutation screening of all the coding regions of CDC20 was performed by Sanger sequencing. The pathogenicity of the identified variants on the CDC20 protein was accessed in silico. Two CDC20 variants, a nonsense mutation p.R262* and a missense mutation p.A211T, identified in one female of 50 unrelated affected individuals, accounting for a relative small proportion of this cohort (2%). In silico analysis revealed that the p.R262* would cause no production of protein or a truncated protein lacking five WD40 repeats in the C-terminus; and that p.A211T may interfere with the formation of a deep hydrophobic pocket and thus disturb the binding of CDC20 protein to the substrates of APC/C. This study identified two novel mutations in CDC20, further expanding the mutation spectrum of this gene. Our findings further confirm that biallelic mutations in CDC20 occur in a proportion of infertile females with oocyte maturation abnormality and early embryonic arrest.//////////////////

Species: human
Mutation name:
type: naturally occurring
fertility: infertile - ovarian defect
Comment: Identification of Novel Mutations in CDC20: Expanding the Mutational Spectrum for Female Infertility. Zhao L et al. (2021) Oocyte maturation and fertilization are fundamental processes for successful human reproduction, and abnormalities in these processes will cause infertility. Recently, we identified biallelic mutations in CDC20 that are responsible for human oocyte maturation arrest, fertilization failure, and early embryonic development arrest. In this study, we screened for further CDC20 mutations in a new cohort of patients with abnormalities in oocyte maturation, fertilization, and early embryonic development. Through whole-exome sequencing, we identified the four novel mutations c.887G > A (p. Arg296Gln), c.964C > T (p.Arg322), c.1155G > C (p.Trp385Cys), and c.330 + 1G > A (p. Glu111Ilefs36) and one previously reported mutation c.965G > A (p.Arg322Gln) in CDC20 in four infertile individuals from three independent families. The patients had different phenotypes of oocyte maturation arrest and fertilization failure resulting from the different mutations. This study confirms our previous research and expands the spectrum of known mutations in CDC20, providing new evidence supporting the function of CDC20 in the genetic etiology of female infertility characterized by oocyte maturation arrest and fertilization failure.//////////////////

Species: human
Mutation name:
type: naturally occurring
fertility: infertile - ovarian defect
Comment: The homozygous p.Tyr228Cys variant in CDC20 causes oocyte maturation arrest: an additional evidence supporting the causality between CDC20 mutation and female infertility. Xu Y et al. (2021)//////////////////

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created: June 20, 2006, 10:38 a.m. by: Alex   email:
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last update: July 7, 2021, 12:22 p.m. by: hsueh    email:



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