RNK komponenta telomeraze, takođe poznata ka TERC, je RNK gen prisutan kod eukariota, koji je komponenta telomeraze, enzima koji produžava telomere.[2][3] TERC služe kao šabloni za telomernu replikaciju (reverznu transkripciju) posredstvom telomeraze. Telomerazne RNK se znatno razlikuju po sekvuenci i strukturi između kičmenjaka, trepljara i kvasaca, mada oni imaju zajedničku strukturu 5' pseudočvora u blizini sekvence šablona. Telomerazna RNA kičmenjaka ima 3' H/ACA domen sličan snoRNK.[4][5][6]
Telomeraza je ribonukleoproteinska polimeraza koja održava telomerne krajeve dodavanjem telomernih ponavljanja TTAGGG. Ovo ponavljanje varira među eukariotama. Enzim se sastoji od proteinske komponente (TERT) sa reverzno transkriptaznom aktivnošću, i RNK komponente, kodirane ovim genom, koja služi kao šablon za telomerno ponavljanje. Izaražavanje telomeraze ima ulogu u ćelijskom starenju, te je normalno zastupljeno u postnatalnim somatskim ćelijama u kojima se javlja progresivno skraćivanje telomera. Deregulacija izražavanja telomeraze u somatskim ćelijama može da doprinese onkogenezi. Studije na miševima sugeriraju da telomeraze takođe učestvuju u hromozomalnoj popravci, pošto do novo sinteze telomernih ponavljanja može doći pri dvolančanim prekidima.[7] Homolozi TERC se takođe mogu naći u Gallid herpes virusima.[8]
Mutacije ovog gena uzrokuju autosomalno dominantni diskeratosis kongenita, i mogu da budu asocirane sa delom slučajeva aplastične anemije.[7]
- ↑ PDB 1ymo; Theimer CA, Blois CA, Feigon J (2005). „Structure of the human telomerase RNA pseudoknot reveals conserved tertiary interactions essential for function.”. Mol Cell 17 (5): 671–82. DOI:10.1016/j.molcel.2005.01.017. PMID 15749017.
- ↑ Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA, Chiu CP, Adams RR, Chang E, Allsopp RC, Yu J (September 1995). „The RNA component of human telomerase”. Science 269 (5228): 1236–41. DOI:10.1126/science.7544491. PMID 7544491.
- ↑ Jády BE, Richard P, Bertrand E, Kiss T (February 2006). „Cell Cycle-dependent Recruitment of Telomerase RNA and Cajal Bodies to Human Telomeres”. Mol. Biol. Cell 17 (2): 944–54. DOI:10.1091/mbc.E05-09-0904. PMC 1356602. PMID 16319170.
- ↑ McCormick-Graham, M; Romero DP (1995). „Ciliate telomerase RNA structural features”. Nucleic Acids Res 23 (7): 1091–1097. DOI:10.1093/nar/23.7.1091. PMC 306816. PMID 7739888.
- ↑ Lingner, J; Hendrick LL, Cech TR (1994). „Telomerase RNAs of different ciliates have a common secondary structure and a permuted template”. Genes Dev 8 (16): 1984–1998. DOI:10.1101/gad.8.16.1984. PMID 7958872.
- ↑ Theimer CA, Feigon J (2006). „Structure and function of telomerase RNA”. Curr. Opin. Struct. Biol. 16 (3): 307–18. DOI:10.1016/j.sbi.2006.05.005. PMID 16713250.
- ↑ 7,0 7,1 „Entrez Gene: TERC telomerase RNA component”.
- ↑ Fragnet, L; Kut E, Rasschaert D (2005). „Comparative functional study of the viral telomerase RNA based on natural mutations”. J Biol Chem. 280 (25): 23502–23515. DOI:10.1074/jbc.M501163200. PMID 15811851.
- de Lange T, Jacks T (1999). „For better or worse? Telomerase inhibition and cancer”. Cell 98 (3): 273–5. DOI:10.1016/S0092-8674(00)81955-8. PMID 10458601.
- Marrone A, Dokal I (2007). „Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer”. Expert reviews in molecular medicine 6 (26): 1–23. DOI:10.1017/S1462399404008671. PMID 15613268.
- Yamaguchi H (2007). „Mutations of telomerase complex genes linked to bone marrow failures”. Journal of Nippon Medical School = Nihon Ika Daigaku zasshi 74 (3): 202–9. DOI:10.1272/jnms.74.202. PMID 17625368.
- Zaug AJ, Linger J, Cech TR (1996). „Method for determining RNA 3' ends and application to human telomerase RNA”. Nucleic Acids Res. 24 (3): 532–3. DOI:10.1093/nar/24.3.532. PMC 145649. PMID 8602368.
- Soder AI, Hoare SF, Muire S i dr.. (1997). „Mapping of the gene for the mouse telomerase RNA component, Terc, to chromosome 3 by fluorescence in situ hybridization and mouse chromosome painting”. Genomics 41 (2): 293–4. DOI:10.1006/geno.1997.4621. PMID 9143511.
- Zhao JQ, Hoare SF, McFarlane R i dr.. (1998). „Cloning and characterization of human and mouse telomerase RNA gene promoter sequences”. Oncogene 16 (10): 1345–50. DOI:10.1038/sj.onc.1201892. PMID 9546436.
- Mitchell JR, Wood E, Collins K (1999). „A telomerase component is defective in the human disease dyskeratosis congenita”. Nature 402 (6761): 551–5. DOI:10.1038/990141. PMID 10591218.
- Chen JL, Blasco MA, Greider CW (2000). „Secondary structure of vertebrate telomerase RNA”. Cell 100 (5): 503–14. DOI:10.1016/S0092-8674(00)80687-X. PMID 10721988.
- Wong KK, Chang S, Weiler SR i dr.. (2000). „Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation”. Nat. Genet. 26 (1): 85–8. DOI:10.1038/79232. PMID 10973255.
- Mitchell JR, Collins K (2000). „Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase”. Mol. Cell 6 (2): 361–71. DOI:10.1016/S1097-2765(00)00036-8. PMID 10983983.
- Imoto I, Pimkhaokham A, Fukuda Y i dr.. (2001). „SNO is a probable target for gene amplification at 3q26 in squamous-cell carcinomas of the esophagus”. Biochem. Biophys. Res. Commun. 286 (3): 559–65. DOI:10.1006/bbrc.2001.5428. PMID 11511096.
- Vulliamy T, Marrone A, Goldman F i dr.. (2001). „The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita”. Nature 413 (6854): 432–5. DOI:10.1038/35096585. PMID 11574891.
- Pruzan R, Pongracz K, Gietzen K i dr.. (2002). „Allosteric inhibitors of telomerase: oligonucleotide N3′→P5′ phosphoramidates”. Nucleic Acids Res. 30 (2): 559–68. DOI:10.1093/nar/30.2.559. PMC 99832. PMID 11788719.
- Zhang RG, Zhang RP, Wang XW, Xie H (2004). „Effects of cisplatin on telomerase activity and telomere length in BEL-7404 human hepatoma cells”. Cell Res. 12 (1): 55–62. DOI:10.1038/sj.cr.7290110. PMID 11942411.
- Yang Y, Chen Y, Zhang C i dr.. (2002). „Nucleolar localization of hTERT protein is associated with telomerase function”. Exp. Cell Res. 277 (2): 201–9. DOI:10.1006/excr.2002.5541. PMID 12083802.
- Chang JT, Chen YL, Yang HT i dr.. (2002). „Differential regulation of telomerase activity by six telomerase subunits”. Eur. J. Biochem. 269 (14): 3442–50. DOI:10.1046/j.1432-1033.2002.03025.x. PMID 12135483.
- Gavory G, Farrow M, Balasubramanian S (2002). „Minimum length requirement of the alignment domain of human telomerase RNA to sustain catalytic activity in vitro”. Nucleic Acids Res. 30 (20): 4470–80. DOI:10.1093/nar/gkf575. PMC 137139. PMID 12384594.
- Sood AK, Coffin J, Jabbari S i dr.. (2003). „p53 null mutations are associated with a telomerase negative phenotype in ovarian carcinoma”. Cancer Biol. Ther. 1 (5): 511–7. PMID 12496479.
- Antal, M; Boros E, Solymosy F, Kiss T (2002). „Analysis of the structure of human telomerase RNA in vivo”. Nucleic Acids Res 30 (4): 912–920. DOI:10.1093/nar/30.4.912. PMC 100349. PMID 11842102.
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Separacija i inicijacija | |
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Replikacija | | DNK polimeraza III holoenzim ( dnaC, dnaE, dnaH, dnaN, dnaQ, dnaT, dnaX, holA, holB, holC, holD, holE) • Replizom • DNK ligaza • DNK stega • Topoizomeraza ( DNK giraza)
Prokariotska DNK polimeraza: DNK polimeraza I ( Klenov fragment) |
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Oba | |
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Terminacija | |
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B bsyn: dnk (repl, cycl, reco, repr) • tscr (fact, tcrg, nucl, rnat, rept, ptts) • tltn (risu, pttl, nexn) • dnab, rnab/runp • stru (domn, 1°, 2°, 3°, 4°) |