Regulation of sister chromatid separation at the metaphase-anaphase transition (Homo sapiens)

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1Ubiquitin-mediateddegradationSpindle checkpoint ONChromosomes attach to spindleChromosomes alignSMC1ACDC20ESPL1MAD1L1MAD2L1BUB1BUB1BBUB3CENPEAPCPTTG1ESPL1PTTG1UbPrometaphaseMetaphaseAnaphaseSeparation of sister chromatidsSMC3RAD21STAG1ESPL1Chromosomes separateSpindle checkpoint OFF


In prometaphase, highly condensed chromosomes establish bipolar attachments to the mitotic spindle. Unattached or mal-orientated chromosomes generate a signal to delay the onset of anaphase until all pairs of sister chromatids are properly aligned on the metaphase plate. This signal is transduced by a relay of spindle-checkpoint proteins, including MAD1, MAD2, BUB1, BUBR1, BUB3 and centrosome protein E (CENPE), which inhibits cell division cycle 20 (CDC20)-mediated activation of an E3 ubiquitin ligase, the anaphase promoting complex/cyclosome (APC/C). Following attachment and alignment of all the chromosomes at metaphase, the checkpoint signal is silenced and APC/C initiates the ubiquitin-dependent degradation of securin and activation of separase. Separase in turn cleaves a multiprotein complex termed cohesin, which creates physical links between sister chromatids to initiate anaphase.

This process may be of interest in colorectal cancer, specifically in terms of the chromosome instability phenotype, which could result from defects in pathways that ensure accurate chromosome segregation. Protein phosphorylation sites were added based on information from PhosphoSitePlus (R),

Adapted from Pino et al.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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  1. Pino MS, Chung DC; ''The chromosomal instability pathway in colon cancer.''; Gastroenterology, 2010 PubMed Europe PMC Scholia


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127399view20:40, 29 September 2023Khansperscorrected gene id
127395view19:46, 29 September 2023Khanspersremoved phospho site
127250view17:38, 28 August 2023KhanspersAdded literature reference and updated description
106495view21:43, 4 September 2019KhanspersModified description
105506view05:58, 8 August 2019KhanspersModified description
96623view17:27, 23 March 2018KhanspersModified description
96621view17:23, 23 March 2018KhanspersOntology Term : 'cell cycle pathway, mitotic' added !
96620view17:20, 23 March 2018KhanspersModified description
96619view17:19, 23 March 2018KhanspersNew pathway

External references


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NameTypeDatabase referenceComment
APCGeneProduct324 (Entrez Gene)
BUB1BGeneProductENSG00000156970 (Ensembl)
BUB1GeneProductENSG00000169679 (Ensembl)
BUB3GeneProductENSG00000154473 (Ensembl)
CDC20GeneProductENSG00000117399 (Ensembl)
CENPEGeneProductENSG00000138778 (Ensembl)
ESPL1GeneProductENSG00000135476 (Ensembl)
MAD1L1GeneProductENSG00000002822 (Ensembl)
MAD2L1GeneProductENSG00000164109 (Ensembl)
PTTG1GeneProductENSG00000164611 (Ensembl)
RAD21GeneProductENSG00000164754 (Ensembl)
SMC1AGeneProductENSG00000072501 (Ensembl)
SMC3GeneProductENSG00000108055 (Ensembl)
STAG1GeneProductENSG00000118007 (Ensembl)

Annotated Interactions

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