7bgb

Structural highlights

Disease

TCAB1_HUMAN Dyskeratosis congenita. The disease is caused by variants affecting the gene represented in this entry.

Function

TCAB1_HUMAN RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies (PubMed:29804836, PubMed:29695869). Specifically recognizes and binds the Cajal body box (CAB box) present in both small Cajal body RNAs (scaRNAs) and telomerase RNA template component (TERC) (PubMed:19285445, PubMed:20351177, PubMed:29804836, PubMed:29695869). Essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex essential for the replication of chromosome termini that elongates telomeres in most eukaryotes (PubMed:19179534, PubMed:20351177, PubMed:26170453, PubMed:29695869). In the telomerase holoenzyme complex, required to stimulate the catalytic activity of the complex (PubMed:27525486, PubMed:29804836). Acts by specifically binding the CAB box of the TERC RNA and controlling the folding of the CR4/CR5 region of the TERC RNA, a critical step for telomerase activity (PubMed:29804836). In addition, also controls telomerase holoenzyme complex localization to Cajal body (PubMed:22547674). During S phase, required for delivery of TERC to telomeres during S phase and for telomerase activity (PubMed:29804836). In addition to its role in telomere maintenance, also required for Cajal body formation, probably by mediating localization of scaRNAs to Cajal bodies (PubMed:19285445, PubMed:21072240). Also plays a role in DNA repair: phosphorylated by ATM in response to DNA damage and relocalizes to sites of DNA double-strand breaks to promote the repair of DNA double-strand breaks (PubMed:25512560, PubMed:27715493). Acts by recruiting the ubiquitin ligase RNF8 to DNA breaks and promote both homologous recombination (HR) and non-homologous end joining (NHEJ) (PubMed:25512560, PubMed:27715493).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]}

See Also

• Telomerase 3D structures

References

1. ↑ Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE. A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science. 2009 Jan 30;323(5914):644-8. PMID:19179534 doi:10.1126/science.1165357
2. ↑ Tycowski KT, Shu MD, Kukoyi A, Steitz JA. A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles. Mol Cell. 2009 Apr 10;34(1):47-57. PMID:19285445 doi:10.1016/j.molcel.2009.02.020
3. ↑ Egan ED, Collins K. Specificity and stoichiometry of subunit interactions in the human telomerase holoenzyme assembled in vivo. Mol Cell Biol. 2010 Jun;30(11):2775-86. PMID:20351177 doi:10.1128/MCB.00151-10
4. ↑ Mahmoudi S, Henriksson S, Weibrecht I, Smith S, Söderberg O, Strömblad S, Wiman KG, Farnebo M. WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies. PLoS Biol. 2010 Nov 2;8(11):e1000521. PMID:21072240 doi:10.1371/journal.pbio.1000521
5. ↑ Stern JL, Zyner KG, Pickett HA, Cohen SB, Bryan TM. Telomerase recruitment requires both TCAB1 and Cajal bodies independently. Mol Cell Biol. 2012 Jul;32(13):2384-95. PMID:22547674 doi:10.1128/MCB.00379-12
6. ↑ Henriksson S, Rassoolzadeh H, Hedström E, Coucoravas C, Julner A, Goldstein M, Imreh G, Zhivotovsky B, Kastan MB, Helleday T, Farnebo M. The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair. Genes Dev. 2014 Dec 15;28(24):2726-38. PMID:25512560 doi:10.1101/gad.246546.114
7. ↑ Vogan JM, Collins K. Dynamics of Human Telomerase Holoenzyme Assembly and Subunit Exchange across the Cell Cycle. J Biol Chem. 2015 Aug 28;290(35):21320-35. PMID:26170453 doi:10.1074/jbc.M115.659359
8. ↑ Vogan JM, Zhang X, Youmans DT, Regalado SG, Johnson JZ, Hockemeyer D, Collins K. Minimized human telomerase maintains telomeres and resolves endogenous roles of H/ACA proteins, TCAB1, and Cajal bodies. Elife. 2016 Aug 15;5:e18221. PMID:27525486 doi:10.7554/eLife.18221
9. ↑ Coucoravas C, Dhanjal S, Henriksson S, Böhm S, Farnebo M. Phosphorylation of the Cajal body protein WRAP53β by ATM promotes its involvement in the DNA damage response. RNA Biol. 2017 Jun 3;14(6):804-813. PMID:27715493 doi:10.1080/15476286.2016.1243647
10. ↑ Nguyen THD, Tam J, Wu RA, Greber BJ, Toso D, Nogales E, Collins K. Cryo-EM structure of substrate-bound human telomerase holoenzyme. Nature. 2018 May;557(7704):190-195. PMID:29695869 doi:10.1038/s41586-018-0062-x
11. ↑ Chen L, Roake CM, Freund A, Batista PJ, Tian S, Yin YA, Gajera CR, Lin S, Lee B, Pech MF, Venteicher AS, Das R, Chang HY, Artandi SE. An Activity Switch in Human Telomerase Based on RNA Conformation and Shaped by TCAB1. Cell. 2018 Jun 28;174(1):218-230.e13. PMID:29804836 doi:10.1016/j.cell.2018.04.039