Page last updated: 2024-10-24

negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of maintenance of mitotic sister chromatid cohesion, telomeric. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:rph, GOC:TermGenie, PMID:26373281]

Negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric, refers to the process of inhibiting or reducing the stability of the protein complexes that hold sister chromatids together at their telomeres during mitosis. Telomeres are specialized structures at the ends of chromosomes that protect them from degradation and fusion. During DNA replication, the telomeres are replicated by a specialized enzyme called telomerase. However, telomerase is not always perfectly efficient, and telomeres can become shorter with each cell division. This shortening can lead to chromosome instability and cell death.

To prevent these problems, cells have evolved mechanisms to maintain telomere length and protect the ends of chromosomes. One important mechanism is the maintenance of mitotic sister chromatid cohesion at telomeres. Sister chromatid cohesion is the process of holding together the two identical copies of a chromosome that are produced during DNA replication. This cohesion is essential for proper chromosome segregation during mitosis, ensuring that each daughter cell receives a complete set of chromosomes.

The protein complexes that mediate sister chromatid cohesion at telomeres are called cohesin complexes. Cohesin complexes are loaded onto chromosomes during DNA replication and remain associated with the chromosomes throughout mitosis. During mitosis, the cohesin complexes are progressively removed from chromosomes, allowing the sister chromatids to separate and migrate to opposite poles of the cell. This process is tightly regulated to ensure that the chromosomes are properly segregated and that each daughter cell receives a complete set of chromosomes.

Negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric, involves the inhibition of cohesin complex function at telomeres. This can be achieved through a variety of mechanisms, such as the recruitment of proteins that can directly interact with cohesin complexes and disrupt their activity, or the activation of signaling pathways that lead to the phosphorylation or ubiquitination of cohesin complex components.

The downregulation of cohesin complex function at telomeres can have several consequences. First, it can lead to premature separation of sister chromatids, resulting in chromosome instability and aneuploidy. Second, it can affect the proper replication of telomeres, leading to telomere shortening and further instability. Finally, it can contribute to the activation of DNA damage response pathways, which can ultimately lead to cell cycle arrest or apoptosis.

In summary, negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric, is a complex process that plays a critical role in regulating chromosome segregation and maintaining genomic stability. It involves the downregulation of cohesin complex function at telomeres, which can be achieved through a variety of mechanisms. Dysregulation of this process can have severe consequences for cell function and can contribute to the development of cancer and other diseases.'
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Proteins (1)

ProteinDefinitionTaxonomy
Poly [ADP-ribose] polymerase tankyrase-1A poly [ADP-ribose] polymerase tankyrase-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95271]Homo sapiens (human)

Compounds (34)

CompoundDefinitionClassesRoles
4'-bromoflavone4'-bromoflavone: structure in first source
phenanthridonephenanthridone : A member of the class of phenanthridines that is phenanthridine with an oxo substituent at position 6. A poly(ADP-ribose) polymerase (PARP) inhibitor, it has been shown to exhibit immunosuppressive activity.

phenanthridone: coal tar derivative; structure given in first source
lactam;
phenanthridines
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
immunosuppressive agent;
mutagen
pj-34PJ34 : A member of the class of phenanthridines that is 5,6-dihydrophenanthridine substituted at positions 2 and 6 by (N,N-dimethylglycyl)amino and oxo groups, respectively. It is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC50 of 110 nM and 86 nM, respectively) and exhibits anti-cancer, cardioprotective and neuroprotective properties.phenanthridines;
secondary carboxamide;
tertiary amino compound
angiogenesis inhibitor;
anti-inflammatory agent;
antiatherosclerotic agent;
antineoplastic agent;
apoptosis inducer;
cardioprotective agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
neuroprotective agent
flavoneflavone : The simplest member of the class of flavones that consists of 4H-chromen-4-one bearing a phenyl substituent at position 2.

flavone: RN given refers to unlabeled cpd; structure given in first source
flavonesmetabolite;
nematicide
4-Methoxybenzamidebenzamides
4'-methoxyflavone4'-methoxyflavone: from seeds of Psoralea corylifolia (Fabaceae); structure in first sourceether;
flavonoids
3',4'-dihydroxyflavone3',4'-dihydroxyflavone: inhibitors of arachidonic acid peroxidation
3-methoxyflavone3-methoxyflavone: from Aspergillus niger; structure in first source
2'-methoxyflavoneether;
flavonoids
6-methoxyflavone6-methoxyflavone: suppresses NFAT-mediated T cell activation; structure in first sourceether;
flavonoids
4'-chloroflavone4'-chloroflavone: structure given in first source
4'-hydroxyflavone4'-hydroxyflavone: structure in first source
6-chloroflavone6-chloroflavone: structure in first source
e-z cinnamic acidcinnamic acid : A monocarboxylic acid that consists of acrylic acid bearing a phenyl substituent at the 3-position. It is found in Cinnamomum cassia.

trans-cinnamic acid : The E (trans) isomer of cinnamic acid
cinnamic acidplant metabolite
7-methoxyflavone7-methoxyflavone: an aromatase inhibitorether;
flavonoids
6-methylflavone6-methylflavone: structure in first source
N-(3-methylphenyl)-4-tetrazolo[1,5-a]quinoxalinaminequinoxaline derivative
iwr-1 exoIWR-1-exo : A dicarboximide having an exo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group. It is a weak axin stabilizer, an analogue of IWR-1-endo.bridged compound;
dicarboximide
axin stabilizer
N-[4-[[[4-(4-methoxyphenyl)-4-oxanyl]methylamino]-oxomethyl]phenyl]-2-furancarboxamidearomatic amide;
furans
apigeninChamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia.trihydroxyflavoneantineoplastic agent;
metabolite
luteolin3'-hydroxyflavonoid;
tetrahydroxyflavone
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
c-Jun N-terminal kinase inhibitor;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
immunomodulator;
nephroprotective agent;
plant metabolite;
radical scavenger;
vascular endothelial growth factor receptor antagonist
3',4',7-trihydroxyflavone3',4',7-trihydroxyflavone: from the Sudanese medicinal plant Albizia zygia; structure in first sourceflavones
rucaparibAG14447: Poly(ADP-ribose) polymerase inhibitor; structure in first sourceazepinoindole;
caprolactams;
organofluorine compound;
secondary amino compound
antineoplastic agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
veliparibbenzimidazolesEC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
N-(4-methylphenyl)-4-tetrazolo[1,5-a]quinoxalinaminequinoxaline derivative
olaparibcyclopropanes;
monofluorobenzenes;
N-acylpiperazine;
phthalazines
antineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
niraparibniraparib : A 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration. It is a potent inhibitor of PARP1 and PARP2 (IC50 of 3.8 and 2.1 nM, respectively) and approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy.

niraparib: structure in first source
2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamideantineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
radiosensitizing agent
iwr-1 endoIWR-1-endo : A dicarboximide having an endo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group.benzamides;
bridged compound;
dicarboximide;
quinolines
axin stabilizer;
Wnt signalling inhibitor
nms-p118NMS-P118: a PARP-1 inhibitor; structure in first source
g007-lkG007-LK: potent and specific small-molecule tankyrase inhibitor; structure in first source
CCT251545CCT251545 : A chloropyridine that is 3-chloropyridine substituted by a 1-oxo-2,8-diazaspiro[4.5]decan-8-yl group and a 4-(1-methyl-1H-pyrazol-4-yl)phenyl group at positions 4 and 5, respectively. It is an orally bioavailable inhibitor of Wnt signaling (IC50 = 5 nM) and a potent and selective chemical probe for cyclin-dependent kinases CDK8 and CDK19.

CCT251545: a Wnt signaling inhibitor; structure in first source
azaspiro compound;
chloropyridine;
pyrazoles
antineoplastic agent;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor;
Wnt signalling inhibitor
xav939XAV939 : 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
2-(4-methoxyphenyl)-1H-quinazolin-4-onequinazolines
bmn 673talazoparib: inhibits both PARP1 and PARP2; structure in first source