Telomere Maintenance (Homo sapiens)

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1, 3, 7-9, 11...161313139132, 4, 6, 10, 14...1319nucleoplasmRPA heterotrimerdCTPG-strand Chromosome end with two additional single strand repeats - TelomericProcessive complex loaded on telomere:Okazaki fragment:Flap:RPA heterotrimer:dna2Telomerase RNP Bound to the Telomeric Chromosome EndATPG-strand chromosome end - TelomericDNA polymerase epsilonTelomerase RNA Component (TERC)Telomerase Holoenzyme Base-paired to the Telomeric Chromosome End with an Additional single Stranded Telomere repeatRFC Heteropentamer:RNA primer-DNA primer:G-strand extended telomere end duplex:PCNA homotrimerRNA primer-DNA primer:G-strand extended telomere:PCNARUVBL2Processive complex loaded on telomere:Okazaki fragment complexNTPExtended And Processed Telomere EndUMPProcessive complex loaded on telomere:Okazaki fragments:Remaining FlapProcessive complex loaded on telomere:Okazaki fragment:FlapdTTPShelterin complexRUVBL1POT1RFC Heteropentamer:RNA primer-DNA primer:G-strand extended telomere endNucleosomeTelomerase RNP Bound and base-paired to the Telomeric Chromosome EndCMPDNA ligase IAMPNHP2RFC HeteropentamerTelomerase RNPRNA primer:G-strand extended telomere end:DNA polymerase alpha:primase complexDKC1TERTDNA polymerase alpha:primaseGMPTCAB1Telomerase RNP:Telomeric Chromosome End with an Additional single Stranded Telomere repeatDNA Polymerase delta tetramerExtended And Processed Telomere End and Associated DNA Binding and Packaging Protein ComplexDNA polymerase alpha:primase:DNA polymerase alpha:G-strand extended telomere endProcessive complex loaded on telomere:nicked DNA from adjacent Okazaki fragmentsProcessive complex loaded on telomerePCNA homotrimerFlap endonuclease-1dna2 endonucleaseProcessive complex loaded on telomere:Okazaki fragment:Flap:RPA heterotrimerProcessive complex loaded on telomere:ligated C-strand Okazaki fragmentsdATPADPdGTPExtended And Processed Telomere End and Associated DNA Binding and Packaging Protein Complex Folded Into Higher Order StructureRNA primer-DNA primer:G-strand extended telomereTelomerase Holoenzyme:Telomeric RNP End with Two Additional Single Stranded Telomere Repeats4512


Description

Telomeres are protein-DNA complexes at the ends of linear chromosomes that are important for genome stability. Telomeric DNA in humans, as in many eukaryotic organisms, consists of tandem repeats (Blackburn and Gall 1978; Moyzis et al. 1988; Meyne et al. 1989). The repeats at human telomeres are composed of TTAGGG sequences and stretch for several kilobase pairs. Another feature of telomeric DNA in many eukaryotes is a G-rich 3' single strand overhang, which in humans is estimated to be approximately 50-300 bases long (Makarov et al. 1997; Wright et al. 1997; Huffman et al. 2000). Telomeric DNA isolated from humans and several other organisms can form a lasso-type structure called a t-loop in which the 3' single-strand end is presumed to invade the double stranded telomeric DNA repeat tract (Griffith et al. 1999). Telomeric DNA is bound by multiple protein factors that play important roles in regulating telomere length and in protecting the chromosome end from recombination, non-homologous end-joining, DNA damage signaling, and unregulated nucleolytic attack (reviewed in de Lange 2005).


DNA attrition can occur at telomeres, which can impact cell viability. Attrition can occur owing to the "end-replication problem", a consequence of the mechanism of lagging-strand synthesis (Watson 1972; Olovnikov 1973). Besides incomplete replication, nucleolytic processing also likely contributes to telomere attrition (Huffman et al. 2000). If telomeres become critically shortened, replicative senescence can result (Harley et al. 1990). Thus, in order to undergo multiple divisions, cells need a mechanism to replenish the sequence at their chromosome ends.


The primary means for maintaining the sequence at chromosome ends in many eukaryotic organisms, including humans, is based on telomerase (Greider and Blackburn, 1985; Morin 1989). Telomerase is a ribonucleoprotein complex minimally composed of a conserved protein subunit containing a reverse transcriptase domain (telomerase reverse transcriptase, TERT) (Lingner et al. 1997; Nakamura et al. 1997) and a template-containing RNA (telomerase RNA component, TERC, TR, TER) (Greider and Blackburn, 1987; Feng et al 1995). Telomerase uses the RNA template to direct addition of multiple tandem repeats to the 3' G-rich single strand overhang. Besides extension by telomerase, maintenance of telomeric DNA involves additional activities, including C-strand synthesis, which fills in the opposing strand, and nucleolytic processing, which likely contributes to the generation of the 3' overhang.

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Bibliography

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History

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114708view16:18, 25 January 2021ReactomeTeamReactome version 75
113153view11:21, 2 November 2020ReactomeTeamReactome version 74
112381view15:31, 9 October 2020ReactomeTeamReactome version 73
101284view11:17, 1 November 2018ReactomeTeamreactome version 66
100821view20:48, 31 October 2018ReactomeTeamreactome version 65
100362view19:23, 31 October 2018ReactomeTeamreactome version 64
99907view16:06, 31 October 2018ReactomeTeamreactome version 63
99463view14:38, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93874view13:42, 16 August 2017ReactomeTeamreactome version 61
93441view11:23, 9 August 2017ReactomeTeamreactome version 61
88407view11:43, 5 August 2016FehrhartOntology Term : 'pathway pertinent to DNA replication and repair, cell cycle, maintenance of genomic integrity, RNA and protein biosynthesis' added !
86532view09:20, 11 July 2016ReactomeTeamreactome version 56
83097view09:58, 18 November 2015ReactomeTeamVersion54
81422view12:57, 21 August 2015ReactomeTeamVersion53
76893view08:16, 17 July 2014ReactomeTeamFixed remaining interactions
76598view11:57, 16 July 2014ReactomeTeamFixed remaining interactions
75930view09:58, 11 June 2014ReactomeTeamRe-fixing comment source
75631view10:50, 10 June 2014ReactomeTeamReactome 48 Update
74986view13:50, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74630view08:41, 30 April 2014ReactomeTeamReactome46
68975view17:41, 8 July 2013MaintBotUpdated to 2013 gpml schema
42143view22:00, 4 March 2011MaintBotAutomatic update
39954view05:58, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
AMP Metabolite16027 (ChEBI)
ATP Metabolite15422 (ChEBI)
CMP Metabolite17361 (ChEBI)
DKC1 ProteinO60832 (UniProt)
DNA Polymerase

delta tetramer

ComplexREACT_5801 (Reactome)
DNA ligase I ProteinP18858 (UniProt)
DNA polymerase

alpha:primase

ComplexREACT_3725 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:G- strand extended telomere end

ComplexREACT_8177 (Reactome)
DNA polymerase

epsilon

ComplexREACT_4621 (Reactome)
Extended And

Processed Telomere End

ComplexREACT_8288 (Reactome)
Extended And

Processed Telomere End and Associated DNA Binding and Packaging Protein Complex

ComplexREACT_8626 (Reactome)
Extended And

Processed Telomere End and Associated DNA Binding and Packaging Protein Complex Folded Into Higher Order Structure

ComplexREACT_8525 (Reactome)
Flap endonuclease-1 ProteinP39748 (UniProt)
G-strand

chromosome end - Telomeric

REACT_8234 (Reactome)
G-strand Chromosome

end with two additional single strand repeats - Telomeric

REACT_8670 (Reactome)
GMP Metabolite17345 (ChEBI)
NHP2 ProteinQ9NX24 (UniProt)
NTP MetaboliteREACT_4491 (Reactome)
Nucleosome ComplexREACT_8671 (Reactome) This is a generic nucleosome created for the telomerase module. It contains Histones H2A, H2B, and H3 as candidate sets where all of the variants of each histone protein are entered as candidates (as opposed to members). The list for each is not exhaustive, but rather is a list of histones known to Reactome at the time of the creation of the nucleosome complex. Histone H4 is only documented once in Uniprot, so for now it is an EWAS.
PCNA homotrimer ComplexREACT_2542 (Reactome)
POT1 ProteinQ9NUX5 (UniProt)
Processive complex

loaded on telomere

ComplexREACT_8041 (Reactome)
Processive complex

loaded on telomere: Okazaki fragment complex

ComplexREACT_8837 (Reactome)
Processive complex

loaded on telomere: Okazaki fragment: Flap

ComplexREACT_8956 (Reactome)
Processive complex

loaded on telomere: Okazaki fragment: Flap:RPA heterotrimer

ComplexREACT_8468 (Reactome)
Processive complex

loaded on telomere: Okazaki fragment: Flap:RPA heterotrimer:dna2

ComplexREACT_8321 (Reactome)
Processive complex

loaded on telomere: Okazaki fragments: Remaining Flap

ComplexREACT_8363 (Reactome)
Processive complex

loaded on telomere: ligated C-strand Okazaki fragments

ComplexREACT_8541 (Reactome)
Processive complex

loaded on telomere: nicked DNA from adjacent Okazaki fragments

ComplexREACT_8309 (Reactome)
RFC

Heteropentamer: RNA primer-DNA primer:G-strand extended telomere end

ComplexREACT_8972 (Reactome)
RFC

Heteropentamer: RNA primer-DNA primer:G-strand extended telomere end duplex:PCNA homotrimer

ComplexREACT_8208 (Reactome)
RFC Heteropentamer ComplexREACT_4881 (Reactome)
RNA primer-DNA

primer:G-strand extended telomere

ComplexREACT_8560 (Reactome)
RNA primer-DNA

primer:G-strand extended telomere: PCNA

ComplexREACT_8843 (Reactome)
RNA primer:G-

strand extended telomere end:DNA polymerase alpha: primase complex

ComplexREACT_8504 (Reactome)
RPA heterotrimer ComplexREACT_3427 (Reactome)
RUVBL1 ProteinQ9Y265 (UniProt)
RUVBL2 ProteinQ9Y230 (UniProt)
Shelterin complex ComplexREACT_8593 (Reactome)
TCAB1 ProteinQ9BUR4 (UniProt)
TERT ProteinO14746 (UniProt)
Telomerase

Holoenzyme Base- paired to the Telomeric Chromosome End with an Additional single Stranded Telomere repeat

ComplexREACT_8180 (Reactome)
Telomerase

Holoenzyme: Telomeric RNP End with Two Additional Single Stranded Telomere Repeats

ComplexREACT_8055 (Reactome)
Telomerase RNA

Component (TERC)

RnaU86046 (EMBL)
Telomerase RNP ComplexREACT_8548 (Reactome)
Telomerase RNP

Bound and base- paired to the Telomeric Chromosome End

ComplexREACT_8909 (Reactome)
Telomerase RNP

Bound to the Telomeric Chromosome End

ComplexREACT_8788 (Reactome)
Telomerase RNP:

Telomeric Chromosome End with an Additional single Stranded Telomere repeat

ComplexREACT_8663 (Reactome)
UMP Metabolite16695 (ChEBI)
dATP Metabolite16284 (ChEBI)
dCTP Metabolite16311 (ChEBI)
dGTP Metabolite16497 (ChEBI)
dTTP Metabolite18077 (ChEBI)
dna2 endonuclease ProteinP51530 (UniProt)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1928"
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