Pathway Human Homo sapiens

DNA Repair

R-HSA-73894 in Reactome release 97: a top-level pathway, with 368 genes placed in it by the mapping files and 7 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-73894 (mouse), R-RNO-73894 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-73894.5
Class: TopLevelPathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2004-07-06
Last updated: 2021-09-15
Events inside: 7, counted from the record

DNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, environmental chemicals and radiation that damage their DNA, thus corrupting genetic information. In addition, normal cellular pH and temperature create conditions that are hostile to the integrity of DNA and its nucleotide components. DNA damage can also arise as a consequence of spontaneous errors during DNA replication. The DNA repair machinery continuously scans the genome and maintains genome integrity by removing or mending any detected damage.

Depending on the type of DNA damage and the cell cycle status, the DNA repair machinery utilizes several different pathways to restore the genome to its original state. When the damage and circumstances are such that the DNA cannot be repaired with absolute fidelity, the DNA repair machinery attempts to minimize the harm and patch the insulted genome well enough to ensure cell viability.

Accumulation of DNA alterations that are the result of cumulative DNA damage and utilization of "last resort" low fidelity DNA repair mechanisms is associated with cellular senescence, aging, and cancer. In addition, germline mutations in DNA repair genes are the underlying cause of many familial cancer syndromes, such as Fanconi anemia, xeroderma pigmentosum, Nijmegen breakage syndrome and Lynch syndrome, to name a few.

When the level of DNA damage exceeds the capacity of the DNA repair machinery, apoptotic cell death ensues. Actively dividing cells have a very limited time available for DNA repair and are therefore particularly sensitive to DNA damaging agents. This is the main rationale for using DNA damaging chemotherapeutic drugs to kill rapidly replicating cancer cells.

There are seven main pathways employed in human DNA repair: DNA damage bypass, DNA damage reversal, base excision repair, nucleotide excision repair, mismatch repair, repair of double strand breaks and repair of interstrand crosslinks (Fanconi anemia pathway). DNA repair pathways are intimately associated with other cellular processes such as DNA replication, DNA recombination, cell cycle checkpoint arrest and apoptosis.

The DNA damage bypass pathway does not remove the damage, but instead allows translesion DNA synthesis (TLS) using a damaged template strand. Translesion synthesis allows cells to complete DNA replication, postponing the repair until cell division is finished. DNA polymerases that participate in translesion synthesis are error-prone, frequently introducing base substitutions and/or small insertions and deletions.

The DNA damage reversal pathway acts on a very narrow spectrum of damaging base modifications to remove modifying groups and restore DNA bases to their original state.

The base excision repair (BER) pathway involves a number of DNA glycosylases that cleave a vast array of damaged bases from the DNA sugar-phosphate backbone. DNA glycosylases produce a DNA strand with an abasic site. The abasic site is processed by DNA endonucleases, DNA polymerases and DNA ligases, the choice of which depends on the cell cycle stage, the identity of the participating DNA glycosylase and the presence of any additional damage. Base excision repair yields error-free DNA molecules.

Mismatch repair (MMR) proteins recognize mismatched base pairs or small insertion or deletion loops during DNA replication and correct erroneous base pairing by excising mismatched nucleotides exclusively from the nascent DNA strand, leaving the template strand intact.

Nucleotide excision repair pathway is involved in removal of bulky lesions that cause distortion of the DNA double helix. NER proteins excise the oligonucleotide that contains the lesion from the affected DNA strand, which is followed by gap-filling DNA synthesis and ligation of the repaired DNA molecule.

Double strand breaks (DSBs) in the DNA can be repaired via a highly accurate homologous recombination repair (HRR) pathway, or through error-prone nonhomologous end joining (NHEJ), single strand annealing (SSA) and microhomology-mediated end joining (MMEJ) pathways. DSBs can be directly generated by some DNA damaging agents, such as X-rays and reactive oxygen species (ROS). DSBs can also be intermediates of the Fanconi anemia pathway.

Interstrand crosslinking (ICL) agents damage the DNA by introducing covalent bonds between two DNA strands, which disables progression of the replication fork. The Fanconi anemia proteins repair the ICLs by unhooking them from one DNA strand. TLS enables the replication fork to bypass the unhooked ICL, resulting in two replicated DNA molecules, one of which contains a DSB and triggers double strand break repair, while the sister DNA molecule contains a bulky unhooked ICL, which is removed through NER.

Single strand breaks (SSBs) in the DNA, generated either by DNA damaging agents or as intermediates of DNA repair pathways such as BER, are converted into DSBs if the repair is not complete prior to DNA replication. Simultaneous inhibition of DSB repair and BER through cancer mutations and anti-cancer drugs, respectively, is synthetic lethal in at least some cancer settings, and is a promising new therapeutic strategy.

For reviews of DNA repair pathways, please refer to Lindahl and Wood 1999 and Curtin 2012.

Literature Reactome attaches

Quality control by DNA repairScience, 1999, vol. 286, p. 1897-905PubMed 10583946
DNA repair dysregulation from cancer driver to therapeutic targetNat. Rev. Cancer, 2012, vol. 12, p. 801-17PubMed 23175119

Reactome's record lists 14 orthologous events, R-MMU-73894 (Mus musculus), R-RNO-73894 (Rattus norvegicus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"DNA Repair". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-73894 with StableID: R-HSA-73894.5 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 368 genes in this human pathway; showing 101 to 200, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 4
Gene	Authority id	Mapping file id	Evidence codes
GeneGTF2H3	AuthorityHGNC:4657	Mapping file id2967 NCBI file	EvidenceTAS
GeneGTF2H4	AuthorityHGNC:4658	Mapping file id2968 NCBI file	EvidenceTAS
GeneGTF2H5	AuthorityHGNC:21157	Mapping file id404672 NCBI file	EvidenceTAS
GeneH2AB1	AuthorityHGNC:22516	Mapping file id474382 NCBI file	EvidenceIEA, TAS
GeneH2AC14	AuthorityHGNC:4727	Mapping file id8331 NCBI file	EvidenceIEA, TAS
GeneH2AC18	AuthorityHGNC:4736	Mapping file id8337 NCBI file	EvidenceIEA, TAS
GeneH2AC19	AuthorityHGNC:29668	Mapping file id723790 NCBI file	EvidenceIEA, TAS
GeneH2AC20	AuthorityHGNC:4738	Mapping file id8338 NCBI file	EvidenceIEA, TAS
GeneH2AC4	AuthorityHGNC:4734	Mapping file id8335 NCBI file	EvidenceIEA, TAS
GeneH2AC6	AuthorityHGNC:4733	Mapping file id8334 NCBI file	EvidenceIEA, TAS
GeneH2AC7	AuthorityHGNC:4729	Mapping file id3013 NCBI file	EvidenceIEA, TAS
GeneH2AC8	AuthorityHGNC:4724	Mapping file id3012 NCBI file	EvidenceIEA, TAS
GeneH2AJ	AuthorityHGNC:14456	Mapping file id55766 NCBI file	EvidenceIEA, TAS
GeneH2AX	AuthorityHGNC:4739	Mapping file id3014 NCBI file	EvidenceIEA, TAS
GeneH2AZ2	AuthorityHGNC:20664	Mapping file id94239 NCBI file	EvidenceIEA, TAS
GeneH2BC1	AuthorityHGNC:18730	Mapping file id255626 NCBI file	EvidenceIEA, TAS
GeneH2BC10	AuthorityHGNC:4756	Mapping file id8346 NCBI file	EvidenceIEA, TAS
GeneH2BC11	AuthorityHGNC:4761	Mapping file id8970 NCBI file	EvidenceIEA, TAS
GeneH2BC12	AuthorityHGNC:13954	Mapping file id85236 NCBI file	EvidenceIEA, TAS
GeneH2BC12L	AuthorityHGNC:4762	Mapping file id54145 NCBI file	EvidenceIEA, TAS
GeneH2BC13	AuthorityHGNC:4748	Mapping file id8340 NCBI file	EvidenceIEA, TAS
GeneH2BC14	AuthorityHGNC:4750	Mapping file id8342 NCBI file	EvidenceIEA, TAS
GeneH2BC15	AuthorityHGNC:4749	Mapping file id8341 NCBI file	EvidenceIEA, TAS
GeneH2BC17	AuthorityHGNC:4758	Mapping file id8348 NCBI file	EvidenceIEA, TAS
GeneH2BC21	AuthorityHGNC:4760	Mapping file id8349 NCBI file	EvidenceIEA, TAS
GeneH2BC26	AuthorityHGNC:20514	Mapping file id128312 NCBI file	EvidenceIEA, TAS
GeneH2BC3	AuthorityHGNC:4751	Mapping file id3018 NCBI file	EvidenceIEA, TAS
GeneH2BC4	AuthorityHGNC:4757	Mapping file id8347 NCBI file	EvidenceIEA, TAS
GeneH2BC5	AuthorityHGNC:4747	Mapping file id3017 NCBI file	EvidenceIEA, TAS
GeneH2BC6	AuthorityHGNC:4753	Mapping file id8344 NCBI file	EvidenceIEA, TAS
GeneH2BC7	AuthorityHGNC:4752	Mapping file id8343 NCBI file	EvidenceIEA, TAS
GeneH2BC8	AuthorityHGNC:4746	Mapping file id8339 NCBI file	EvidenceIEA, TAS
GeneH2BC9	AuthorityHGNC:4755	Mapping file id8345 NCBI file	EvidenceIEA, TAS
GeneH3-4	AuthorityHGNC:4778	Mapping file id8290 NCBI file	EvidenceIEA, TAS
GeneH4C1	AuthorityHGNC:4781	Mapping file id8359 NCBI file	EvidenceIEA, TAS
GeneH4C11	AuthorityHGNC:4785	Mapping file id8363 NCBI file	EvidenceIEA, TAS
GeneH4C12	AuthorityHGNC:4784	Mapping file id8362 NCBI file	EvidenceIEA, TAS
GeneH4C13	AuthorityHGNC:4791	Mapping file id8368 NCBI file	EvidenceIEA, TAS
GeneH4C14	AuthorityHGNC:4794	Mapping file id8370 NCBI file	EvidenceIEA, TAS
GeneH4C15	AuthorityHGNC:29607	Mapping file id554313 NCBI file	EvidenceIEA, TAS
GeneH4C16	AuthorityHGNC:20510	Mapping file id121504 NCBI file	EvidenceIEA, TAS
GeneH4C2	AuthorityHGNC:4789	Mapping file id8366 NCBI file	EvidenceIEA, TAS
GeneH4C3	AuthorityHGNC:4787	Mapping file id8364 NCBI file	EvidenceIEA, TAS
GeneH4C4	AuthorityHGNC:4782	Mapping file id8360 NCBI file	EvidenceIEA, TAS
GeneH4C5	AuthorityHGNC:4790	Mapping file id8367 NCBI file	EvidenceIEA, TAS
GeneH4C6	AuthorityHGNC:4783	Mapping file id8361 NCBI file	EvidenceIEA, TAS
GeneH4C8	AuthorityHGNC:4788	Mapping file id8365 NCBI file	EvidenceIEA, TAS
GeneH4C9	AuthorityHGNC:4793	Mapping file id8294 NCBI file	EvidenceIEA, TAS
GeneHERC2	AuthorityHGNC:4868	Mapping file id8924 NCBI file	EvidenceTAS
GeneHUS1	AuthorityHGNC:5309	Mapping file id3364 NCBI file	EvidenceTAS
GeneINO80	AuthorityHGNC:26956	Mapping file id54617 NCBI file	EvidenceTAS
GeneINO80B	AuthorityHGNC:13324	Mapping file id83444 NCBI file	EvidenceTAS
GeneINO80C	AuthorityHGNC:26994	Mapping file id125476 NCBI file	EvidenceTAS
GeneINO80D	AuthorityHGNC:25997	Mapping file id54891 NCBI file	EvidenceTAS
GeneINO80E	AuthorityHGNC:26905	Mapping file id283899 NCBI file	EvidenceTAS
GeneISG15	AuthorityHGNC:4053	Mapping file id9636 NCBI file	EvidenceTAS
GeneISY1	AuthorityHGNC:29201	Mapping file id57461 NCBI file	EvidenceTAS
GeneISY1-RAB43	AuthorityHGNC:42969	Mapping file id100534599 NCBI file	EvidenceTAS
GeneKAT5	AuthorityHGNC:5275	Mapping file id10524 NCBI file	EvidenceTAS
GeneKDM4A	AuthorityHGNC:22978	Mapping file id9682 NCBI file	EvidenceTAS
GeneKDM4B	AuthorityHGNC:29136	Mapping file id23030 NCBI file	EvidenceTAS
GeneKPNA2	AuthorityHGNC:6395	Mapping file id3838 NCBI file	EvidenceTAS
GeneLIG1	AuthorityHGNC:6598	Mapping file id3978 NCBI file	EvidenceTAS
GeneLIG3	AuthorityHGNC:6600	Mapping file id3980 NCBI file	EvidenceTAS
GeneLIG4	AuthorityHGNC:6601	Mapping file id3981 NCBI file	EvidenceTAS
GeneMAD2L2	AuthorityHGNC:6764	Mapping file id10459 NCBI file	EvidenceTAS
GeneMAPK8	AuthorityHGNC:6881	Mapping file id5599 NCBI file	EvidenceTAS
GeneMBD4	AuthorityHGNC:6919	Mapping file id8930 NCBI file	EvidenceTAS
GeneMCRS1	AuthorityHGNC:6960	Mapping file id10445 NCBI file	EvidenceTAS
GeneMDC1	AuthorityHGNC:21163	Mapping file id9656 NCBI file	EvidenceTAS
GeneMGMT	AuthorityHGNC:7059	Mapping file id4255 NCBI file	EvidenceTAS
GeneMLH1	AuthorityHGNC:7127	Mapping file id4292 NCBI file	EvidenceIEA, TAS
GeneMNAT1	AuthorityHGNC:7181	Mapping file id4331 NCBI file	EvidenceTAS
GeneMPG	AuthorityHGNC:7211	Mapping file id4350 NCBI file	EvidenceTAS
GeneMRE11	AuthorityHGNC:7230	Mapping file id4361 NCBI file	EvidenceTAS
GeneMSH2	AuthorityHGNC:7325	Mapping file id4436 NCBI file	EvidenceIEA, TAS
GeneMSH3	AuthorityHGNC:7326	Mapping file id4437 NCBI file	EvidenceIEA, TAS
GeneMSH6	AuthorityHGNC:7329	Mapping file id2956 NCBI file	EvidenceTAS
GeneMUS81	AuthorityHGNC:29814	Mapping file id80198 NCBI file	EvidenceTAS
GeneMUTYH	AuthorityHGNC:7527	Mapping file id4595 NCBI file	EvidenceTAS
GeneNBN	AuthorityHGNC:7652	Mapping file id4683 NCBI file	EvidenceTAS
GeneNEIL1	AuthorityHGNC:18448	Mapping file id79661 NCBI file	EvidenceTAS
GeneNEIL2	AuthorityHGNC:18956	Mapping file id252969 NCBI file	EvidenceTAS
GeneNEIL3	AuthorityHGNC:24573	Mapping file id55247 NCBI file	EvidenceIEA, TAS
GeneNFRKB	AuthorityHGNC:7802	Mapping file id4798 NCBI file	EvidenceTAS
GeneNHEJ1	AuthorityHGNC:25737	Mapping file id79840 NCBI file	EvidenceTAS
GeneNPLOC4	AuthorityHGNC:18261	Mapping file id55666 NCBI file	EvidenceTAS
GeneNSD2	AuthorityHGNC:12766	Mapping file id7468 NCBI file	EvidenceTAS
GeneNTHL1	AuthorityHGNC:8028	Mapping file id4913 NCBI file	EvidenceTAS
GeneOGG1	AuthorityHGNC:8125	Mapping file id4968 NCBI file	EvidenceTAS
GenePALB2	AuthorityHGNC:26144	Mapping file id79728 NCBI file	EvidenceTAS
GenePARG	AuthorityHGNC:8605	Mapping file id8505 NCBI file	EvidenceTAS
GenePARP1	AuthorityHGNC:270	Mapping file id142 NCBI file	EvidenceTAS
GenePARP2	AuthorityHGNC:272	Mapping file id10038 NCBI file	EvidenceTAS
GenePAXIP1	AuthorityHGNC:8624	Mapping file id22976 NCBI file	EvidenceTAS
GenePCLAF	AuthorityHGNC:28961	Mapping file id9768 NCBI file	EvidenceTAS
GenePCNA	AuthorityHGNC:8729	Mapping file id5111 NCBI file	EvidenceIEA, TAS
GenePHF6	AuthorityHGNC:18145	Mapping file id84295 NCBI file	EvidenceTAS
GenePIAS1	AuthorityHGNC:2752	Mapping file id8554 NCBI file	EvidenceTAS
GenePIAS3	AuthorityHGNC:16861	Mapping file id10401 NCBI file	EvidenceTAS

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

None: this is a top-level pathway of the release.

Children

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.