Telomeres and Telomere Length: A General Overview
Abstract
:1. Introduction
2. Telomere-Associated Proteins
2.1. Nucleosomes
2.2. Shelterin Complex
2.3. Other Telomere-Interacting Complexes
2.4. Subtelomeres
3. Telomere End Replication Problem
4. Mechanisms of Telomere Maintenance
4.1. Telomerase Structure and Biogenesis
4.2. Telomerase Reactivation
4.2.1. Gene Amplification of TERT and TERC and Rearrangement of TERT
4.2.2. TERT Promoter Mutations
4.2.3. Epigenetic Mechanisms
4.3. Alternative Lengthening of Telomeres
5. Telomere Length Heritability
5.1. Genetic Factors Associated with Telomere Length
Genes (Locus) | SNP a | Genomic Position (GR37/hg19) b | ΔTL c | p-Value d | Reference |
---|---|---|---|---|---|
TERC (3q26.2) | rs1317082 rs10936601 rs12696304 rs16847897 rs10936599 rs3772190 | 3:169497585 3:169528449 3:169481271 3:169568116 3:169492101 3:169500487 | (−) 77 bp NA (−) 75 bp (−) 33 bp NA NA | 1 × 10−8 4 × 10−15 4 × 10−14 1 × 10−5 3 × 10−31 2 × 10−1 | [178] [178] [179] [179] [180] [186] |
OBFC1 (10q24) | rs2487999 rs9420907 rs4387287 rs9419958 | 10:105659826 10:105676465 10:105677897 10:105675946 | (+) 100 bp NA (−) 230 bp NA | 4 × 10−14 7 × 10−11 2 × 10−11 9 × 10−11 | [178] [180] [181] [182] |
TERT (5p15.3) | rs7726159 rs2736100 rs2736108 rs7705526 rs2853669 | 5:1282319 5:1286516 5:1297488 5:1285974 5:1295349 | (+) 73 bp (−) 94 bp NA (+) 90 bp (+) 60 bp | 5 × 10−17 4 × 10−6 5 × 10−5 1 × 10−15 - | [178] [180] [194] [194] |
PXK (3p14.4) | rs6772228 | 3:58376019 | (−) 120 bp | 4 × 10−10 | [178] |
ZNF311 (6p22.1) | rs9257445 | 6:28949206 | (−) 38 bp | 1 × 10−7 | [178] |
BCL2L1 (20q11.2) | rs6060627 | 20:30262159 | (+) 36 bp | 6 × 10−7 | [178] |
GRIA4 (11q22.3) | rs610160 | 11:105696895 | (+) 30 bp | 7 × 10−6 | [179] |
NAF1 (4q32.2) | rs7675998 | 4:164007820 | (−) 90bp | 4 × 10−16 | [180] |
RTEL1 (20q13.3) | rs755017 | 20:62421622 | (−) 74 bp | 7 × 10−9 | [180] |
ACYP2 (2p16.2) | rs11125529 | 2:54475866 | (−) 67 bp | 8 × 10−10 | [180] |
ZNF208 (19p12) | rs8105767 | 19:22215441 | (−) 58 bp | 1 × 10−9 | [180] |
MPHOSPH6 (16q23.3) | rs2967374 | 16:82209861 | NA | 3 × 10−7 | [180] |
CTC1 (17p13.1) | rs3027234 | 17:8136092 | (−) 57 bp | 2 × 10−8 | [182] |
ZNF676 (19p12) | rs412658 | 19:22359440 | (−) 49 bp | 1 × 10−8 | [182] |
DCAF4 (14q24.2) | rs2535913 | 14: 73415233 | (−) 45 bp | 2 × 10−7 | [195] |
DHX35 (20q11.23) | rs6028466 | 20:38129002 | NA | 3 × 10−7 | [183] |
DKK2 (4q25) | rs7680468 | 4:108304199 | NA | 5 × 10−8 | [184] |
CSNKA2 (16q21) | rs74019828 | 16:58209274 | (−) 38 bp | 5 × 10−8 | [190] |
Functionality of Telomere Length-Associated Single Nucleotide Polymorphisms
5.2. Environmental Factors Affecting Telomere Length
6. Telomere Length and Risk of Cancers
7. Telomeres as Potential Targets for Anti-Cancer Therapy
8. Conclusions
Author contributions
Funding
Conflicts of Interest
References
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Srinivas, N.; Rachakonda, S.; Kumar, R. Telomeres and Telomere Length: A General Overview. Cancers 2020, 12, 558. https://doi.org/10.3390/cancers12030558
Srinivas N, Rachakonda S, Kumar R. Telomeres and Telomere Length: A General Overview. Cancers. 2020; 12(3):558. https://doi.org/10.3390/cancers12030558
Chicago/Turabian StyleSrinivas, Nalini, Sivaramakrishna Rachakonda, and Rajiv Kumar. 2020. "Telomeres and Telomere Length: A General Overview" Cancers 12, no. 3: 558. https://doi.org/10.3390/cancers12030558