DNA Damage Bypass (Homo sapiens)

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1-3REV1:damaged DNAtemplate complex[nucleoplasm]REV1:lesioned DNAtemplate withmisinserted bases[nucleoplasm]Pol zeta complex[nucleoplasm]Pol eta:lesioned DNAtemplate insertedwith correct basecomplement[nucleoplasm]Pol zeta complex[nucleoplasm]Pol eta:damaged DNAtemplate complex[nucleoplasm]Pol zeta:damaged DNAtemplate complex[nucleoplasm]nucleoplasmPOLH [nucleoplasm]dNTPPol zeta:damaged DNAtemplate complexMAD2L2REV1 [nucleoplasm]hREV3(1-?)[nucleoplasm]Pol zeta complexREV1REV1:damaged DNAtemplate complexREV1:lesioned DNAtemplate withmisinserted baseshREV3(1-?)Pol eta:lesioned DNAtemplate insertedwith correct basecomplementMAD2L2 [nucleoplasm]POLHElongated DNAtemplate withbypassed lesionMAD2L2 [nucleoplasm]POLH [nucleoplasm]hREV3(1-?)[nucleoplasm]damaged DNAsubstratePol eta:damaged DNAtemplate complexREV1 [nucleoplasm]


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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CompareRevisionActionTimeUserComment
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

View all...
NameTypeDatabase referenceComment
Elongated DNA

template with

bypassed lesion		REACT_3182 (Reactome)
MAD2L2 [nucleoplasm]ProteinQ9UI95 (Uniprot-TrEMBL)
MAD2L2ProteinQ9UI95 (Uniprot-TrEMBL)
POLH [nucleoplasm]ProteinQ9Y253 (Uniprot-TrEMBL)
POLHProteinQ9Y253 (Uniprot-TrEMBL)
Pol eta:damaged DNA template complexComplexREACT_2831 (Reactome)
Pol eta:lesioned DNA

template inserted with correct base

complement		ComplexREACT_3971 (Reactome)
Pol zeta complexComplexREACT_5310 (Reactome)
Pol zeta:damaged DNA template complexComplexREACT_5394 (Reactome)
REV1 [nucleoplasm]ProteinQ9UBZ9 (Uniprot-TrEMBL)
REV1:damaged DNA template complexComplexREACT_3664 (Reactome)
REV1:lesioned DNA

template with

misinserted bases		ComplexREACT_5530 (Reactome)
REV1ProteinQ9UBZ9 (Uniprot-TrEMBL)
dNTPREACT_2960 (Reactome)
damaged DNA substrateREACT_2765 (Reactome)
hREV3(1-?) [nucleoplasm]ProteinQ9UID5 (Uniprot-TrEMBL)
hREV3(1-?)ProteinQ9UID5 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
Elongated DNA

template with

bypassed lesion		ArrowREACT_1324 (Reactome)
Elongated DNA

template with

bypassed lesion		ArrowREACT_1479 (Reactome)
Elongated DNA

template with

bypassed lesion		ArrowREACT_867 (Reactome)
MAD2L2REACT_1544 (Reactome)
POLHArrowREACT_1479 (Reactome)
POLHREACT_504 (Reactome)
Pol eta:damaged DNA template complexArrowREACT_504 (Reactome)
Pol eta:damaged DNA template complexREACT_2016 (Reactome)
Pol eta:damaged DNA template complexmim-catalysisREACT_2016 (Reactome)
Pol eta:lesioned DNA

template inserted with correct base

complement		ArrowREACT_2016 (Reactome)
Pol eta:lesioned DNA

template inserted with correct base

complement		REACT_1479 (Reactome)
Pol eta:lesioned DNA

template inserted with correct base

complement		mim-catalysisREACT_1479 (Reactome)
Pol zeta complexArrowREACT_1324 (Reactome)
Pol zeta complexArrowREACT_1544 (Reactome)
Pol zeta complexREACT_1918 (Reactome)
Pol zeta:damaged DNA template complexArrowREACT_1918 (Reactome)
Pol zeta:damaged DNA template complexREACT_1324 (Reactome)
Pol zeta:damaged DNA template complexmim-catalysisREACT_1324 (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 complexArrowREACT_1502 (Reactome)
REV1:damaged DNA template complexREACT_2214 (Reactome)
REV1:damaged DNA template complexmim-catalysisREACT_2214 (Reactome)
REV1:lesioned DNA

template with

misinserted bases		ArrowREACT_2214 (Reactome)
REV1:lesioned DNA

template with

misinserted bases		REACT_867 (Reactome)
REV1:lesioned DNA

template with

misinserted bases		mim-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)
hREV3(1-?)REACT_1544 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1803"
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