Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of sister chromatid cohesion in the centromeric region of a chromosome. [GOC:mah]
Centromeric sister chromatid cohesion is a crucial process that ensures accurate chromosome segregation during cell division. This process involves the establishment and maintenance of a physical connection between sister chromatids, which are identical copies of a chromosome that are generated during DNA replication. The cohesion complex, a multi-protein assembly, plays a pivotal role in maintaining this connection.
The establishment of cohesion is initiated during DNA replication. The cohesin complex, composed of four core subunits (SMC1, SMC3, SCC1, and SCC3), is loaded onto chromosomes. Cohesin forms ring-like structures that encircle sister chromatids, effectively holding them together.
During prophase of mitosis, the cohesion complex is gradually removed from chromosome arms, allowing for the separation of sister chromatids. However, cohesion is maintained at the centromere, the specialized region of the chromosome that serves as the attachment site for microtubules.
The centromeric cohesion is crucial for the proper segregation of sister chromatids to opposite poles of the cell. The protease separase, which is activated during anaphase, cleaves the SCC1 subunit of the cohesin complex, leading to the release of sister chromatids and their subsequent segregation.
The regulation of centromeric sister chromatid cohesion is a complex and highly regulated process. The timing of cohesion establishment, maintenance, and removal is critical for ensuring accurate chromosome segregation. It is also important to ensure that cohesion is only released from the centromere when the chromosomes are properly attached to microtubules, preventing the formation of lagging chromosomes and aneuploidy.
Several factors contribute to the regulation of centromeric cohesion, including:
* **Shugoshin**: A protein that protects centromeric cohesion from separase-mediated cleavage during early mitosis.
* **Aurora B kinase**: An enzyme that phosphorylates cohesin and other centromeric proteins, facilitating cohesion removal at the onset of anaphase.
* **Microtubule attachment**: The proper attachment of chromosomes to microtubules signals the activation of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets separase for degradation, leading to the release of sister chromatids.
In summary, the regulation of centromeric sister chromatid cohesion is a tightly controlled process that ensures the accurate segregation of chromosomes during cell division. Any defects in this process can lead to chromosome missegregation and aneuploidy, which are associated with various diseases, including cancer.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Axin-2 | An Axin-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y2T1] | Homo sapiens (human) |
| Catenin beta-1 | A catenin beta-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35222] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| salvin | salvin: a biocyclic diterpenoid; from sage and rosemary (Lamiaceae) | abietane diterpenoid; carbotricyclic compound; catechols; monocarboxylic acid | angiogenesis modulating agent; anti-inflammatory agent; antineoplastic agent; antioxidant; apoptosis inducer; food preservative; HIV protease inhibitor; plant metabolite |
| toxoflavin | toxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7. toxoflavin: azapteridine antibiotic; structure | carbonyl compound; pyrimidotriazine | antibacterial agent; antineoplastic agent; apoptosis inducer; bacterial metabolite; toxin; virulence factor; Wnt signalling inhibitor |
| cercosporin | cercosporin : An organic heterohexacyclic compound that is perylo[1,12-def][1,3]dioxepine-6,11-dione substituted by hydroxy groups at positions 5 and 12, by methoxy groups at positions 7 and 10, and by 2-hydroxypropyl groups at positions 8 and 9 (the R,R-stereoisomer). It is a phytotoxin which was first isolated from the pathogenic soybean fungus, Cercospora kikuchii and later found in multiple members of the genus Cercospora. cercosporin: phyytotoxin from Cercospora beticola Sacc; posses photodynamic action on mice, bacteria & plants | ||
| LSM-42773 | aromatic ketone | ||
| etodolac, (-)-isomer | (R)-etodolac : The R-enantiomer of etodolac. It is inactive, in contrast to the enantiomer, (S)-etodolac, which is a preferential inhibitor of cyclo-oxygenase 2 and a non-steroidal anti-inflammatory. The racemate is commonly used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. | etodolac | |
| ucn 1028 c | calphostin C: structure given in first source; isolated from Cladosporium cladosporioides | ||
| xav939 | XAV939 : A thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group. XAV939: selectively inhibits beta-catenin-mediated transcription; structure in first source | (trifluoromethyl)benzenes; thiopyranopyrimidine | tankyrase inhibitor |