Mitotic Metaphase and Anaphase (Homo sapiens)
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Description
Metaphase is marked by the formation of the metaphase plate. The metaphase plate is formed when the spindle fibers align the chromosomes along the middle of the cell. Such an organization helps to ensure that later, when the chromosomes are separated, each new nucleus that is formed receives one copy of each chromosome. This pathway has not yet been annotated in Reactome.
The metaphase to anaphase transition during mitosis is triggered by the destruction of mitotic cyclins.
In anaphase, the paired chromosomes separate at the centromeres, and move to the opposite sides of the cell. The movement of the chromosomes is facilitated by a combination of kinetochore movement along the spindle microtubules and through the physical interaction of polar microtubules. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2555396
The metaphase to anaphase transition during mitosis is triggered by the destruction of mitotic cyclins.
In anaphase, the paired chromosomes separate at the centromeres, and move to the opposite sides of the cell. The movement of the chromosomes is facilitated by a combination of kinetochore movement along the spindle microtubules and through the physical interaction of polar microtubules. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2555396
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History
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External references
DataNodes
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Annotated Interactions
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| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| 26S proteasome | mim-catalysis | REACT_6777 (Reactome)  | ||
| ANKLE2 | Arrow | REACT_160246 (Reactome) | ||
| ANKLE2 | REACT_160159 (Reactome) | |||
| Ac-CoA | Arrow | REACT_150294 (Reactome) | ||
| BANF1 | Arrow | REACT_160246 (Reactome) | ||
| BANF1 | REACT_160075 (Reactome) | |||
| CDC20
p-APC/C PTTG1 | REACT_6723 (Reactome) | |||
| CDC20 p-APC/C | Arrow | REACT_6777 (Reactome) | ||
| CDC20 p-APC/C | REACT_6893 (Reactome) | |||
| CDC20 p-APC/C | mim-catalysis | REACT_6723 (Reactome) | ||
| Chromatin | REACT_160075 (Reactome) | |||
| Cleaved Cohesin
PDS5 WAPAL | Arrow | REACT_150148 (Reactome) | ||
| Cleaved Cohesin
PDS5 WAPAL | REACT_150294 (Reactome) | |||
| CoA-SH | REACT_150294 (Reactome) | |||
| Cohesin Complex | Arrow | REACT_150294 (Reactome) | ||
| EMD/ TMPO/ LEMD3/ LEMD2 | REACT_160075 (Reactome) | |||
| ESPL1 Autocleaved | mim-catalysis | REACT_150369 (Reactome) | ||
| ESPL1 | REACT_150297 (Reactome) | |||
| ESPL1 | mim-catalysis | REACT_150308 (Reactome) | ||
| H2O | REACT_160246 (Reactome) | |||
| HDAC8 | mim-catalysis | REACT_150294 (Reactome) | ||
| Lamin dimers | REACT_160075 (Reactome) | |||
| PDS5 | Arrow | REACT_150294 (Reactome) | ||
| PLK1 | mim-catalysis | REACT_496 (Reactome) | ||
| PP2A | mim-catalysis | REACT_160246 (Reactome) | ||
| PTTG1 | REACT_150297 (Reactome) | |||
| PTTG1 | REACT_6893 (Reactome) | |||
| Pi | Arrow | REACT_160246 (Reactome) | ||
| RAD21 | Arrow | REACT_150294 (Reactome) | ||
| RAD21 | REACT_150294 (Reactome) | |||
| REACT_150148 (Reactome) | The cleavage of RAD21 subunit of centromeric cohesin by ESPL1 (separin i.e. separase) promotes dissociation of cohesin complexes from centromeric chromatin at the onset of anaphase, allowing for sister chromatid separation and segregation of replicated chromosomes to daughter cells (Waizenegger et al. 2000, Hauf et al. 2001, Waizenegger et al. 2002). | |||
| REACT_150294 (Reactome) | Histone deacetylase HDAC8 deacetylates SMC3 cohesin subunit. SMC3 deacetylation promotes dissociation of cleaved RAD21 fragments from other cohesin proteins and their replacement with intact RAD21, thereby allowing restoration of the cohesin complex (Deardorff et al. 2012). HDAC8 mutations, as well as mutations in NIPBL, SMC1A and SMC3, can cause Cornelia de Lang syndrome (Deardorff et al. 2012). | |||
| REACT_150297 (Reactome) | Up to anaphase onset, ESPL1 (separase i.e. separin) forms a complex with PTTG1 (pituitary tumor-transforming gene 1) i.e. securin. PTTG1 sequesters ESPL1 and block its catalytic site, preventing it from cleaving centromeric cohesin and causing premature separation of sister chromatids (Zou et al. 1999, Waizenegger et al. 2001, Waizenegger et al. 2002). PTTG1 is overexpressed in cancer and acts as an oncogene (Zhang et al. 1999). Regulation of PTTG1 cellular level is important for chromosomal stability in human cells (Jallepalli et al. 2001). | |||
| REACT_150308 (Reactome) | After APC/C-mediated degradation of PTTG1 (securin), ESPL1 (separin i.e. separase) is rapidly autocatalytically cleaved after arginine residues at positions 1506 and 1535. The N-terminal and C-terminal fragments remain bound to each other after cleavage. It has not been examined what happens with the short middle fragment of ESPL1, so it is annotated as a part of the autocleaved ESPL1 complex. The autocatalytic cleavage of ESPL1 is not a prerequisite for the subsequent cleavage of the cohesin subunit RAD21 (Waizenegger et al. 2002). | |||
| REACT_150369 (Reactome) | ESPL1 (separin i.e. separase) cleaves RAD21 (SCC1) subunit of centromeric cohesin at two sites that conform to the consensus separase recognition site E-X-X-R: after arginine residue R172 and after arginine residue R450 (Hauf et al. 2001). Phosphorylation of RAD21 at the serine residue S454 by PLK1 in prometaphase facilitates ESPL1-mediated cleavage of RAD21 at the C-terminal cleavage site R450 (Hauf et al. 2005). The N-terminal and C-terminal RAD21 cleavage fragments remain bound to the rest of the cohesin complex (Deardorff et al. 2012). It is not clear whether RAD21 middle fragment also continues to be associated with cohesin. | |||
| REACT_160075 (Reactome) | In late anaphase/early telophase, dephosphorylated BANF1 (BAF) accumulates at a specialized region of the separated chromosome mass, close to the spindle. This region is known as the 'core' and is the central region of the assembling nuclear rim. At the 'core', BANF1 (BAF) binds chromatin, LEM-domain proteins of the inner nuclear membrane (EMD i.e. emerin, TMPO i.e. LAP2beta, LEMD3 i.e. MAN1, LEMD2 i.e. LEM2) and lamins, which initiates the reassembly of the nuclear envelope around separated sister chromatids. LEM-domain proteins and lamin A accumulate at the 'core' in a BANF1-dependent manner (Haraguchi et al. 2001, Haraguchi et al. 2008, Asencio et al. 2012). | |||
| REACT_160159 (Reactome) | ANKLE2 (LEM4) is required for nuclear envelope formation in C. elegans and its function appears to be conserved in human cells. Both human LEM4 and the C. elegans ortholog bind VRK1 (and possibly VRK2), the kinase responsible for phosphorylation of BANF1 (BAF) in mitotic prophase, and inhibit VRK1 catalytic activity (Asencio et al. 2012). | |||
| REACT_160246 (Reactome) | The PP2A complex that contains the regulatory subunit B55-alpha (PPP2R2A) is the only phosphatase essential for mitotic exit (Schmitz et al. 2010). The PP2A complex is necessary for BANF1 (BAF) dephosphorylation in late mitotic anaphase. ANKLE2 (LEM4) binds the PP2A complex that contains the B55-alpha regulatory subunit and facilitates BANF1 dephosphorylation, but as ANKLE2 does not interact with BANF1 (BAF) directly, the exact mechanism has not been determined (Asencio et al. 2012). | |||
| REACT_496 (Reactome) | During the early stages of mitosis, Cdc2 and PLK1 cooperate to phosphorylate Emi1 and this modification induces Emi1 degradation through a Skp1-Cullin1 F-box protein (SCF) ubiquitin ligase-mediated proteolysis. Degradation of Emi1 permits activation of anaphase promoting complex and thereby the onset of anaphase. | |||
| REACT_6723 (Reactome) | Securin is ubiquitinated by APC/C:Cdc20 (Hagting et al., 2002; Jin et al. 2008). | |||
| REACT_6777 (Reactome) | Following ubiquitination, securin is degraded by the 26S proteasome. | |||
| REACT_6893 (Reactome) | Securin is thought to be recognized by the APC/C:Cdc20 complex through its conserved D-box sequence. | |||
| Sister Centromere
Kinetochore Microtubules | Arrow | REACT_150148 (Reactome) | ||
| Ub | Arrow | REACT_6777 (Reactome) | ||
| Ub | REACT_6723 (Reactome) | |||
| VRK1/VRK2 | REACT_160159 (Reactome) | |||
| WAPAL | Arrow | REACT_150294 (Reactome) | ||
| p-S21,S75,T159-CDCA5 | Arrow | REACT_150148 (Reactome) | ||
| p-S454-RAD21 | Arrow | REACT_150294 (Reactome) | ||
| p-T2,T3,S4-BANF1 | REACT_160246 (Reactome) |
