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telomerase

Function: - RNA-dependent DNA polymerase - adds repeated arrays of the sequence TTAGGG to 5'ends of linear DNA to form telomeres. - maintains telomere ends during replicative DNA synthesis - telomerase contains an RNA template as an integral component of the enzyme complex - DNA replication proceeding in the 5'-> 3' direction requires an RNA primer for intitiation, therefore it leaves a stretch of unreplicated DNA at the 5'end of linear DNA - this leads to a loss of terminal telomeric repeats with every S-phase, with shortening of telomeres ~100 base pairs per cell division. - in germ cell lines & in some tissues, telomere length is maintained by telomerase activity - in many cells & tissues, telomerase activity is low or absent resulting in telomere loss with each cell division - this limits the replicative capacity of cells, but also prevents outgrowth of a transformed cell into an immortal malignant cell. Structure: - subunits include TERT, DKC1, WRAP53/TCAB1, NOP10, NHP2, GAR1, TEP1, EST1A, POT1 & a telomerase RNA template component (TERC) * 3D structure [9] Pathology: - activation of telomerase has been implicated in cell immortalization & cancer cell pathogenesis - inhibition has been suggested to play a role in aging, however, more likely plays a role in terminal differentiation

Related

telomere telomeres & telomerase in tumor cells

General

multisubunit protein RNA-dependent DNA polymerase

Properties

COMPARTMENT: cell nucleus MOTIF: active site SUBUNITS: telomerase catalytic chain COMPARTMENT: cell nucleus MOTIF: Reverse transcriptase {605-935} Thr phosphorylation site {T1113} Ser phosphorylation site {S1125} H/ACA ribonucleoprotein complex subunit 4 COMPARTMENT: cell nucleus MOTIF: Nucleolar localization {2-21} acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl lysine-rich region {11-17} MOTIF: lysine residue (SEVERAL) Ser phosphorylation site {S21} aspartate residue {D125} PUA {296-371} Ser phosphorylation site {S422} Nuclear and nucleolar localization {446-514} MOTIF: Ser phosphorylation site {S451} Ser phosphorylation site {S453} Ser phosphorylation site {S455} Thr phosphorylation site {T458} Ser phosphorylation site {S485} Ser phosphorylation site {S494} Thr phosphorylation site {T496} Thr phosphorylation site {T497} Ser phosphorylation site {S513} WD repeat protein 79 COMPARTMENT: cytoplasm cell nucleus MOTIF: proline-rich region SITE: 8-57 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S26} Ser phosphorylation site {S30} Ser phosphorylation site {S54} Ser phosphorylation site {S64} Ser phosphorylation site {S85} Ser phosphorylation site {S90} Ser phosphorylation site {S112} Ser phosphorylation site {S114} WD repeat {167-206} WD repeat {222-267} WD repeat {272-313} WD repeat {323-364} WD repeat {365-405} WD repeat {411-450} Thr phosphorylation site {T489} Ser phosphorylation site {S491} ribosome biogenesis protein Nop10 COMPARTMENT: cell nucleus H/ACA ribonucleoprotein complex subunit 2 COMPARTMENT: cell nucleus GAR1 telomerase protein component 1 MOTIF: TEP1 {1-30} TEP1 {31-60} TEP1 {61-90} TEP1 {91-120} TROVE {223-676} NACHT domain NAME: NACHT domain SITE: 1162-1490 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 1168-1175 WD repeat {1411-1448} WD repeat {1674-2098} (10) WD repeat {2105-2626} (10) telomerase-binding protein EST1A COMPARTMENT: cell nucleus MOTIF: telomeric DNA interaction {114-503} MOTIF: coiled coil {163-193} coiled coil {567-625} coiled coil {1197-1239} manganese [Mn]-binding site SITE: 1251-1251 manganese [Mn]-binding site SITE: 1353-1353 manganese [Mn]-binding site SITE: 1392-1392 POT1 protein COMPARTMENT: cell nucleus MOTIF: DNA-binding motif telomerase RNA template

References

  1. Hoeijmakers JH Genome maintenance mechanisms for preventing cancer. Nature 411:366, 2001 PMID: 11357144
  2. Campisi J Aging and cancer: the double-edged sword of replicative senescence. J Am Geriatr Soc 45:482, 1997 PMID: 9100719
  3. Dahse R et al Telomeres and telomerase: biological and clinical importance. Clin Chem 43:708, 1997 PMID: 9166220
  4. Ershler WB & Longo DL The biology of aging: the current research agenda. Cancer 89:1284, 1997 PMID: 9317181
  5. Fossel M Telomerase and the aging cell: implications for human health. JAMA 279:1732, 1998 PMID: 9624027
  6. Jaskelioff M et al Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature. 2011 Jan 6;469(7328):102-6. Epub 2010 Nov 28. PMID: 21113150 http://www.nature.com/nature/journal/v469/n7328/full/nature09603.html
  7. UniProt :accession Q9NUX5
  8. Cong Y, Shay JW Actions of human telomerase beyond telomeres. Cell Research (2008) 18:725-732 PMID: 18574498 http://www.nature.com/cr/journal/v18/n7/full/cr200874a.html
  9. Sanders R. Long-sought structure of telomerase paves way for drugs for aging, cancer. UC Berkeley News. April 25, 2018 http://news.berkeley.edu/2018/04/25/long-sought-structure-of-telomerase-paves-way-for-drugs-for-aging-cancer/

Components

H/ACA ribonucleoprotein complex subunit 2 (nucleolar protein family A member 2, snoRNP protein NHP2, NOLA2, NHP2, HSPC286) H/ACA ribonucleoprotein complex subunit 4; dyskerin; nucleolar protein family A member 4; snoRNP protein DKC1; Nopp140-associated protein of 57 kDa; nucleolar protein NAP57; CBF5 homolog (DKC1, NOLA4) POT1 protein (protection of telomeres 1, POT1-like telomere end-binding protein) ribosome biogenesis protein Nop10; H/ACA ribonucleoprotein complex subunit 3; snoRNP protein NOP10; nucleolar protein family A member 3 (NOP10, NOLA3) telomerase catalytic chain or telomerase reverse transcriptase telomerase protein component 1 (TEP1, p240, p80 telomerase homolog) telomerase RNA template component (TER, TERC) telomerase-binding protein EST1A; ever shorter telomeres 1A; telomerase subunit EST1A (EST1A, SMG6, C17orf31, KIAA0732) WD repeat protein 79; telomerase Cajal body protein 1; WD40 repeat-containing protein encoding RNA antisense to p53 (WRAP53 TCAB1 WDR79)