negative regulation of double-strand break repair via single-strand annealing
Definition
Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of double-strand break repair via single-strand annealing. [GOC:sart, GOC:TermGenie]
Negative regulation of double-strand break repair via single-strand annealing is a critical process that ensures precise repair of DNA damage while preventing the formation of harmful rearrangements. This pathway involves the suppression of the canonical homologous recombination (HR) mechanism, which relies on extensive homology between the broken DNA ends.
In the absence of extensive homology, cells utilize single-strand annealing (SSA) as an alternative repair pathway. SSA involves the annealing of complementary single-stranded DNA (ssDNA) regions flanking the break. This process is facilitated by specific enzymes, including the RecA/Rad51 recombinase family, which promotes strand invasion and exchange. However, excessive SSA can lead to deletions and loss of genetic information, as the process relies on limited homology between the two broken ends.
Negative regulation of SSA is essential to prevent its uncontrolled activation and ensure the fidelity of DNA repair. This regulation is achieved through a series of intricate mechanisms:
1. **Suppression of 5' end resection**: SSA requires the 5' end of the broken DNA to be resected, exposing single-stranded DNA for annealing. Enzymes like the Mre11-Rad50-Nbs1 (MRN) complex, involved in the initial stages of double-strand break processing, can be negatively regulated to limit resection and suppress SSA.
2. **Inhibition of strand invasion**: The annealing of complementary ssDNA regions is catalyzed by recombinases. Specific factors, such as the RAD52 protein, can inhibit this process by blocking strand invasion and preventing the formation of the recombination intermediate.
3. **Promoting alternative pathways**: Negative regulation of SSA can also occur by promoting alternative repair pathways, such as non-homologous end joining (NHEJ), which relies on the direct ligation of broken DNA ends. This shift towards NHEJ ensures the efficient repair of double-strand breaks without relying on extensive homology.
Overall, the negative regulation of double-strand break repair via single-strand annealing is a complex process involving multiple regulatory mechanisms that ensure precise repair while preventing detrimental genetic rearrangements.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| N-glycosylase/DNA lyase | An N-glycosylase/DNA lyase that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15527] | Homo sapiens (human) |
Compounds (5)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| hydralazine | hydralazine : The 1-hydrazino derivative of phthalazine; a direct-acting vasodilator that is used as an antihypertensive agent. Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. | azaarene; hydrazines; ortho-fused heteroarene; phthalazines | antihypertensive agent; vasodilator agent |
| isocarboxazid | Isocarboxazid: An MAO inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. (From AMA, Drug Evaluations Annual, 1994, p311) | benzenes | |
| isoniazid | Hydra: A genus of freshwater polyps in the family Hydridae, order Hydroida, class HYDROZOA. They are of special interest because of their complex organization and because their adult organization corresponds roughly to the gastrula of higher animals. hydrazide : Compounds derived from oxoacids RkE(=O)l(OH)m (l =/= 0) by replacing -OH by -NRNR2 (R groups are commonly H). (IUPAC). | carbohydrazide | antitubercular agent; drug allergen |
| nialamide | Nialamide: An MAO inhibitor that is used as an antidepressive agent. | organonitrogen compound; organooxygen compound | |
| hydralazine hydrochloride | hydralazine hydrochloride : The hydrochloride salt of hydralazine; a direct-acting vasodilator that is used as an antihypertensive agent. | hydrochloride | antihypertensive agent; vasodilator agent |