DNA Damage Bypass (Homo sapiens)

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1-3Pol zeta complex REV1damaged DNA template complex REV1lesioned DNA template with misinserted bases Pol zetadamaged DNA template complex Pol etalesioned DNA template inserted with correct base complement nucleoplasmPol zeta complex Pol etadamaged DNA template complex REV1hREV3POLH hREV3MAD2L2REV1 Pol zetadamaged DNA template complexPol zeta complexPol etadamaged DNA template complexdamaged DNA substratehREV3MAD2L2 dNTPREV1damaged DNA template complexPOLH Pol etalesioned DNA template inserted with correct base complementREV1 POLHElongated DNA template with bypassed lesionREV1lesioned DNA template with misinserted basesMAD2L2


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. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=73893

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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 lesionREACT_3182 (Reactome)
MAD2L2 ProteinQ9UI95 (Uniprot-TrEMBL)
MAD2L2ProteinQ9UI95 (Uniprot-TrEMBL)
POLH ProteinQ9Y253 (Uniprot-TrEMBL)
POLHProteinQ9Y253 (Uniprot-TrEMBL)
Pol eta damaged DNA template complexComplexREACT_2831 (Reactome)
Pol eta lesioned DNA template inserted with correct base complementComplexREACT_3971 (Reactome)
Pol zeta damaged DNA template complexComplexREACT_5394 (Reactome)
Pol zeta complexComplexREACT_5310 (Reactome)
REV1 damaged DNA template complexComplexREACT_3664 (Reactome)
REV1 lesioned DNA template with misinserted basesComplexREACT_5530 (Reactome)
REV1 ProteinQ9UBZ9 (Uniprot-TrEMBL)
REV1ProteinQ9UBZ9 (Uniprot-TrEMBL)
dNTPREACT_2960 (Reactome)
damaged DNA substrateREACT_2765 (Reactome)
hREV3ProteinQ9UID5 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
Elongated DNA template with bypassed lesionArrowREACT_1324 (Reactome)
Elongated DNA template with bypassed lesionArrowREACT_1479 (Reactome)
Elongated DNA template with bypassed lesionArrowREACT_867 (Reactome)
MAD2L2REACT_1544 (Reactome)
POLHArrowREACT_1479 (Reactome)
POLHREACT_504 (Reactome)
Pol eta damaged DNA template complexmim-catalysisREACT_2016 (Reactome)
Pol eta lesioned DNA template inserted with correct base complementmim-catalysisREACT_1479 (Reactome)
Pol zeta damaged DNA template complexREACT_1324 (Reactome)
Pol zeta damaged DNA template complexmim-catalysisREACT_1324 (Reactome)
Pol zeta complexArrowREACT_1324 (Reactome)
Pol zeta complexREACT_1918 (Reactome)
REACT_1324 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', and 1 molecule of 'Pol zeta:damaged DNA template complex' are present. At the end of this reaction, 1 molecule of 'Pol zeta complex', and 1 molecule of 'Elongated DNA template with bypassed lesion' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'Pol zeta:damaged DNA template complex'.

REACT_1479 (Reactome) At the beginning of this reaction, 1 molecule of 'Pol eta:lesioned DNA template inserted with correct base complement' is present. At the end of this reaction, 1 molecule of 'Pol eta protein', and 1 molecule of 'Elongated DNA template with bypassed lesion' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'eta DNA polymerase activity' of 'Pol eta:lesioned DNA template inserted with correct base complement'.

REACT_1502 (Reactome) At the beginning of this reaction, 1 molecule of 'damaged DNA substrate ', and 1 molecule of 'HREV1 protein' are present. At the end of this reaction, 1 molecule of 'HREV1:damaged DNA template complex' is present.

This reaction takes place in the 'nucleus'.

REACT_1544 (Reactome) At the beginning of this reaction, 1 molecule of 'HREV7', and 1 molecule of 'HREV3' are present. At the end of this reaction, 1 molecule of 'Pol zeta complex' is present.

This reaction takes place in the 'nucleus'.

REACT_1918 (Reactome) At the beginning of this reaction, 1 molecule of 'damaged DNA substrate ', and 1 molecule of 'Pol zeta complex' are present. At the end of this reaction, 1 molecule of 'Pol zeta:damaged DNA template complex' is present.

This reaction takes place in the 'nucleus'.

REACT_2016 (Reactome) At the beginning of this reaction, 1 molecule of 'Pol eta:damaged DNA template complex' is present. At the end of this reaction, 1 molecule of 'Pol eta:lesioned DNA template inserted with correct base complement' is present.

This reaction takes place in the 'nucleus' and is mediated by the 'eta DNA polymerase activity' of 'Pol eta:damaged DNA template complex'.

REACT_2214 (Reactome) At the beginning of this reaction, 1 molecule of 'HREV1:damaged DNA template complex' is present. At the end of this reaction, 1 molecule of 'HREV1:lesioned DNA template with misinserted bases' is present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'HREV1:damaged DNA template complex'.

REACT_504 (Reactome) At the beginning of this reaction, 1 molecule of 'damaged DNA substrate ', and 1 molecule of 'Pol eta protein' are present. At the end of this reaction, 1 molecule of 'Pol eta:damaged DNA template complex' is present.

This reaction takes place in the 'nucleus'.

REACT_867 (Reactome) At the beginning of this reaction, 1 molecule of 'HREV1:lesioned DNA template with misinserted bases' is present. At the end of this reaction, 1 molecule of 'HREV1 protein', and 1 molecule of 'Elongated DNA template with bypassed lesion' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'HREV1:lesioned DNA template with misinserted bases'.

REV1 damaged DNA template complexmim-catalysisREACT_2214 (Reactome)
REV1 lesioned DNA template with misinserted basesmim-catalysisREACT_867 (Reactome)
REV1ArrowREACT_867 (Reactome)
REV1REACT_1502 (Reactome)
dNTPREACT_1324 (Reactome)
damaged DNA substrateREACT_1502 (Reactome)
damaged DNA substrateREACT_1918 (Reactome)
damaged DNA substrateREACT_504 (Reactome)
hREV3REACT_1544 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1803"
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