Page last updated: 2024-10-24

DNA double-strand break processing involved in repair via single-strand annealing

Definition

Target type: biologicalprocess

The 5' to 3' exonucleolytic resection of the DNA at the site of the break to form a 3' single-strand DNA overhang that results in the repair of a double strand break via single-strand annealing. [GOC:dph, GOC:tb]

DNA double-strand breaks (DSBs) are highly deleterious lesions that can lead to genomic instability and cell death if not repaired efficiently. Single-strand annealing (SSA) is a homologous recombination (HR) pathway that repairs DSBs by using homologous sequences located on the same or sister chromatid. SSA is a relatively simple pathway compared to other HR pathways, involving only a few key steps.

1. **Resection**: Following DSB formation, 5' to 3' exonucleases, such as EXO1 and BLM, resect the 5' ends of the broken DNA strands, generating 3' single-stranded tails.

2. **Annealing**: The 3' single-stranded tails from both ends of the DSB invade the homologous sequence on the other broken DNA strand, forming a "D-loop" structure. This process is facilitated by the RAD52 protein, which promotes annealing of the complementary single-stranded tails.

3. **Ligation**: The annealed DNA strands are ligated together by DNA ligases, such as LIG1, to form a single continuous DNA molecule.

4. **Gap Repair**: The gaps in the newly synthesized DNA are filled in by DNA polymerase, using the other strand as a template.

5. **Deletion**: SSA repair typically results in the deletion of the DNA sequence between the two homologous regions that were used for annealing. This is because the sequences between the break points are not replicated during the repair process.

SSA repair is particularly important for repairing DSBs that occur within repetitive sequences, such as microsatellites. These sequences are prone to deletions and insertions, which can lead to genomic instability. SSA can repair these DSBs without the need for extensive homology searching, which is required for other HR pathways. However, SSA repair is also prone to errors, as the deletion of sequences can disrupt gene function.

In summary, SSA repair is a specialized HR pathway that repairs DSBs by using homologous sequences located on the same or sister chromatid. This process involves resection of the broken DNA ends, annealing of the single-stranded tails, ligation of the annealed strands, gap repair, and deletion of the sequence between the homologous regions. SSA is particularly important for repairing DSBs within repetitive sequences, but it is also prone to errors, as the deletion of sequences can disrupt gene function.'
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Proteins (1)

ProteinDefinitionTaxonomy
DNA repair protein RAD52 homologA DNA repair protein RAD52 homolog that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (17)

CompoundDefinitionClassesRoles
aurintricarboxylic acidaurintricarboxylic acid : A member of the class of quinomethanes that is 3-methylidene-6-oxocyclohexa-1,4-diene-1-carboxylic acid in which the methylidene hydrogens are replaced by 4-carboxy-3-hydroxyphenyl groups. The trisodium salt is the biological stain 'chrome violet CG' while the triammonium salt is 'aluminon'.

Aurintricarboxylic Acid: A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues.
monohydroxybenzoic acid;
quinomethanes;
tricarboxylic acid
fluorochrome;
histological dye;
insulin-like growth factor receptor 1 antagonist
gossypolGossypol: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer.
oxidopamineoxidopamine : A benzenetriol that is phenethylamine in which the hydrogens at positions 2, 4, and 5 on the phenyl ring are replaced by hydroxy groups. It occurs naturally in human urine, but is also produced as a metabolite of the drug DOPA (used for the treatment of Parkinson's disease).

Oxidopamine: A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.
benzenetriol;
catecholamine;
primary amino compound
drug metabolite;
human metabolite;
neurotoxin
1,2,5,8-tetrahydroxy anthraquinone1,2,5,8-tetrahydroxy anthraquinone: structure in first source

quinalizarin : A tetrahydroxyanthraquinone having the four hydroxy groups at the 1-, 2-, 5- and 8-positions.
tetrahydroxyanthraquinoneEC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor
epigallocatechin gallate(-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.

epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis)
flavans;
gallate ester;
polyphenol
antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
epicatechin(-)-epicatechin : A catechin with (2R,3R)-configuration.catechin;
polyphenol
antioxidant
gallocatechol(-)-epigallocatechin : A flavan-3,3',4',5,5',7-hexol having (2R,3R)-configuration.catechin;
flavan-3,3',4',5,5',7-hexol
antioxidant;
food component;
plant metabolite
strictininstrictinin: antioxidant from green tea leaves (Camellia sinensis L.); structure in first source
corilagincorilagin : An ellagitannin with a hexahydroxydiphenoyl group bridging over the 3-O and 6-O of the glucose core.

corilagin: isolated from Geranii herba
ellagitannin;
gallate ester
antihypertensive agent;
antioxidant;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor;
non-steroidal anti-inflammatory drug
6-hydroxydopa6-hydroxydopa: RN given refers to cpd without isomeric designationnon-proteinogenic alpha-amino acid
epicatechin gallate(-)-epicatechin-3-O-gallate : A gallate ester obtained by formal condensation of the carboxy group of gallic acid with the (3R)-hydroxy group of epicatechin. A natural product found in Parapiptadenia rigida.

epicatechin gallate: a steroid 5alpha-reductase inhibitor; RN given refers to the (cis)-isomer; structure given in first source; isolated from green tea
catechin;
gallate ester;
polyphenol
EC 3.2.1.1 (alpha-amylase) inhibitor;
EC 3.2.1.20 (alpha-glucosidase) inhibitor;
metabolite
asiatic acidmonocarboxylic acid;
pentacyclic triterpenoid;
triol
angiogenesis modulating agent;
metabolite
gossypetingossypetin : A hexahydroxyflavone having the hydroxy groups placed at the 3-, 3'-, 4'-, 5- 7- and 8-positions.

gossypetin: inhibits activity of penicillinase enzyme in E coli
7-hydroxyflavonol;
hexahydroxyflavone
plant metabolite
3-(4-chlorophenyl)-1-methyl-N-[3-(1-pyrrolidinyl)propyl]-5-thieno[2,3-c]pyrazolecarboxamidepyrazoles;
ring assembly
cedrelonecedrelone: from Toona ciliata; structure in first sourcelimonoid
rolitetracyclinerolitetracycline : A derivative of tetracycline in which the amide function is substituted with a pyrrolidinomethyl group.

Rolitetracycline: A pyrrolidinylmethyl TETRACYCLINE.
methacycline monohydrochloride