Pathway Human Homo sapiens

HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)

R-HSA-5693567 in Reactome release 97: under Homology Directed Repair, with 135 genes placed in it by the mapping files and 3 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-5693567 (mouse), R-RNO-5693567 (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-5693567.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2003-11-03
Last updated: 2022-04-07
Events inside: 3, counted from the record

Homology directed repair (HDR) of replication-independent DNA double-strand breaks (DSBs) via homologous recombination repair (HRR) or single strand annealing (SSA) requires the activation of ATM followed by ATM-mediated phosphorylation of DNA repair proteins. ATM coordinates the recruitment of DNA repair and signaling proteins to DSBs and formation of the so-called ionizing radiation induced foci (IRIF). While IRIFs include chromatin regions kilobases away from the actual DSB, this Reactome pathway represents simplified foci and shows events that happen at the very ends of the broken DNA.

For both HRR and SSA to occur, the ends of the DNA DSB must be processed (resected) to generate lengthy 3' ssDNA tails, and the resulting ssDNA coated with RPA complexes, triggering ATR activation and signaling.

After the resection step, BRCA2 and RAD51 trigger HRR, a very accurate process in which the 3'-ssDNA overhang invades a sister chromatid, base pairs with the complementary strand of the sister chromatid DNA duplex, creating a D-loop, and uses the complementary sister chromatid strand as a template for DNA repair synthesis that bridges the DSB.

The SSA is triggered when 3'-ssDNA overhangs created in the resection step contain highly homologous direct repeats. In a process involving RAD52, the direct repeats in each 3'-ssDNA overhang become annealed, the unannealed 3'-flaps excised, and structures then processed by DNA repair synthesis. SSA results in the loss of one of the annealed repeats and the DNA sequence between the two repeats. Therefore, SSA is error-prone and is probably used as a backup for HRR, with RAD52 loss-of-function mutations being synthetically lethal with mutations in HRR genes, such as BRCA2 (reviewed by Ciccia and Elledge 2010).

Literature Reactome attaches

The DNA damage response: making it safe to play with knivesMol. Cell, 2010, vol. 40, p. 179-204PubMed 20965415

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 135 genes in this human pathway; showing 101 to 135, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneRFC4	AuthorityHGNC:9972	Mapping file id5984 NCBI file	EvidenceTAS
GeneRFC5	AuthorityHGNC:9973	Mapping file id5985 NCBI file	EvidenceTAS
GeneRHNO1	AuthorityHGNC:28206	Mapping file id83695 NCBI file	EvidenceTAS
GeneRMI1	AuthorityHGNC:25764	Mapping file id80010 NCBI file	EvidenceTAS
GeneRMI2	AuthorityHGNC:28349	Mapping file id116028 NCBI file	EvidenceTAS
GeneRNF168	AuthorityHGNC:26661	Mapping file id165918 NCBI file	EvidenceTAS
GeneRNF4	AuthorityHGNC:10067	Mapping file id6047 NCBI file	EvidenceTAS
GeneRNF8	AuthorityHGNC:10071	Mapping file id9025 NCBI file	EvidenceTAS
GeneRPA1	AuthorityHGNC:10289	Mapping file id6117 NCBI file	EvidenceTAS
GeneRPA2	AuthorityHGNC:10290	Mapping file id6118 NCBI file	EvidenceTAS
GeneRPA3	AuthorityHGNC:10291	Mapping file id6119 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceTAS
GeneRTEL1	AuthorityHGNC:15888	Mapping file id51750 NCBI file	EvidenceTAS
GeneSEM1	AuthorityHGNC:10845	Mapping file id7979 NCBI file	EvidenceTAS
GeneSIRT6	AuthorityHGNC:14934	Mapping file id51548 NCBI file	EvidenceTAS
GeneSLX1A	AuthorityHGNC:20922	Mapping file id548593 NCBI file	EvidenceTAS
GeneSLX1B	AuthorityHGNC:28748	Mapping file id79008 NCBI file	EvidenceTAS
GeneSLX4	AuthorityHGNC:23845	Mapping file id84464 NCBI file	EvidenceTAS
GeneSPIDR	AuthorityHGNC:28971	Mapping file id23514 NCBI file	EvidenceTAS
GeneSUMO2	AuthorityHGNC:11125	Mapping file id6613 NCBI file	EvidenceTAS
GeneTIMELESS	AuthorityHGNC:11813	Mapping file id8914 NCBI file	EvidenceTAS
GeneTIPIN	AuthorityHGNC:30750	Mapping file id54962 NCBI file	EvidenceTAS
GeneTOP3A	AuthorityHGNC:11992	Mapping file id7156 NCBI file	EvidenceTAS
GeneTOPBP1	AuthorityHGNC:17008	Mapping file id11073 NCBI file	EvidenceTAS
GeneTP53BP1	AuthorityHGNC:11999	Mapping file id7158 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceTAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceTAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceTAS
GeneUBE2I	AuthorityHGNC:12485	Mapping file id7329 NCBI file	EvidenceTAS
GeneUBE2N	AuthorityHGNC:12492	Mapping file id7334 NCBI file	EvidenceTAS
GeneUBE2V2	AuthorityHGNC:12495	Mapping file id7336 NCBI file	EvidenceTAS
GeneUIMC1	AuthorityHGNC:30298	Mapping file id51720 NCBI file	EvidenceTAS
GeneWRN	AuthorityHGNC:12791	Mapping file id7486 NCBI file	EvidenceTAS
GeneXRCC2	AuthorityHGNC:12829	Mapping file id7516 NCBI file	EvidenceTAS
GeneXRCC3	AuthorityHGNC:12830	Mapping file id7517 NCBI file	EvidenceTAS

Evidence codes on this page: 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

Homology Directed RepairR-HSA-5693538141 genes

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.