DNA Damage Bypass (Homo sapiens)

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1-3nucleoplasmdNTPPol eta:lesioned DNA template inserted with correct base complementElongated DNA template with bypassed lesionPol eta proteinHREV1:lesioned DNA template with misinserted basesHREV7Pol zeta complexHREV3HREV1:damaged DNA template complexdamaged DNA substrateHREV1Pol eta:damaged DNA template complexPol zeta:damaged DNA template complex


Description

In addition to various processes for removing damaging lesions from the DNA, cells have developed specific mechanisms for tolerating unexcised damages during the replication of the genome. Such processes are collectively called DNA damage bypass pathways. Several proteins including novel Y-family polymerases that have been recently identified in multitude of organisms are involved in this process.
Translesion synthesis (TLS) or replicative bypass of damaged bases that are known to arrest high fidelity, highly processive polymerases involved in DNA replication is carried out by error-prone polymerases Pol zeta, Pol eta and Rev3 protein among others. TLS is implicated in UV and chemical induced mutagenesis of normal human cells where lesions in the replicating genome are carried over to the newly formed daughter cells.
All these 3 enzymes are found to lack 3’->5’ exonuclease activity, while exhibiting low fidelity, weak processivity and sufficient polymerase activities. An outline of the bypass synthesis by these 3 enzymes is annotated here. Complete details of damage recognition and discrimination, initiation of specific polymerase activity and the finer mechanisms are yet to be elucidated.

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Bibliography

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History

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115091view17:04, 25 January 2021ReactomeTeamReactome version 75
113533view12:01, 2 November 2020ReactomeTeamReactome version 74
112731view16:13, 9 October 2020ReactomeTeamReactome version 73
101647view11:51, 1 November 2018ReactomeTeamreactome version 66
101183view21:39, 31 October 2018ReactomeTeamreactome version 65
100709view20:11, 31 October 2018ReactomeTeamreactome version 64
100259view16:56, 31 October 2018ReactomeTeamreactome version 63
99812view15:20, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99356view12:48, 31 October 2018ReactomeTeamreactome version 62
93950view13:47, 16 August 2017ReactomeTeamreactome version 61
93543view11:26, 9 August 2017ReactomeTeamreactome version 61
86644view09:23, 11 July 2016ReactomeTeamreactome version 56
83335view10:49, 18 November 2015ReactomeTeamVersion54
81489view13:01, 21 August 2015ReactomeTeamVersion53
76966view08:24, 17 July 2014ReactomeTeamFixed remaining interactions
76671view12:03, 16 July 2014ReactomeTeamFixed remaining interactions
76000view10:05, 11 June 2014ReactomeTeamRe-fixing comment source
75703view11:04, 10 June 2014ReactomeTeamReactome 48 Update
75059view13:57, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74703view08:46, 30 April 2014ReactomeTeamReactome46
45195view10:04, 7 October 2011MartijnVanIerselOntology Term : 'DNA repair pathway' added !
42026view21:51, 4 March 2011MaintBotAutomatic update
39829view05:51, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
Elongated DNA

template with bypassed lesion

UnknownREACT_3182 (Reactome)
HREV1 ProteinREACT_14374 (Reactome)
HREV1:damaged

DNA template complex

ComplexREACT_3664 (Reactome)
HREV1:lesioned

DNA template with misinserted bases

ComplexREACT_5530 (Reactome)
HREV3 ProteinQ9UID5 (UniProt)
HREV7 ProteinQ9UI95 (UniProt)
Pol eta protein ProteinQ9Y253 (UniProt)
Pol eta:damaged DNA

template complex

ComplexREACT_2831 (Reactome)
Pol eta:lesioned DNA

template inserted with correct base complement

ComplexREACT_3971 (Reactome)
Pol zeta complex ComplexREACT_5310 (Reactome)
Pol zeta:damaged

DNA template complex

ComplexREACT_5394 (Reactome)
dNTP UnknownREACT_2960 (Reactome)
damaged DNA

substrate

UnknownREACT_2765 (Reactome)

Annotated Interactions

No annotated interactions

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