nucleotide-excision repair complex
Definition
Target type: cellularcomponent
Any complex formed of proteins that act in nucleotide-excision repair. [PMID:10915862]
The nucleotide-excision repair (NER) complex is a multi-protein machinery responsible for removing bulky DNA lesions, such as UV-induced pyrimidine dimers and chemical adducts. It operates in two distinct sub-pathways: global genome NER (GG-NER) and transcription-coupled NER (TC-NER). Both pathways share a common core machinery, but differ in how they recognize the DNA damage.
GG-NER involves a series of proteins that scan the entire genome for lesions. The process begins with the recognition of the damaged DNA by a complex of proteins, including XPC, RAD23B, and CENT2. This complex binds to the lesion and recruits additional factors, such as TFIIH, a complex that contains helicases and kinases. TFIIH unwinds the DNA around the lesion, exposing it to the endonucleases XPF-ERCC1 and XPG. These endonucleases make incisions on either side of the damaged DNA, excising the damaged segment. The gap is then filled in by DNA polymerase and sealed by DNA ligase.
TC-NER is specifically triggered by the blockage of RNA polymerase during transcription. RNA polymerase encounters the damaged DNA and stalls. This triggers the recruitment of a specialized complex containing CSA and CSB, which helps recruit the core NER machinery. The downstream steps of DNA unwinding, excision, and repair are similar to those in GG-NER.
The cellular component of the NER complex includes a variety of proteins that function as:
* **Damage recognition and binding:** XPC, RAD23B, CENT2, CSA, CSB, and XPA.
* **DNA unwinding:** TFIIH (containing helicases XPB and XPD).
* **Endonuclease activity:** XPF-ERCC1 and XPG.
* **DNA synthesis:** DNA polymerases (e.g., polymerase δ and ε).
* **DNA ligation:** DNA ligase.
The NER complex operates within the nucleus, primarily associating with chromatin and DNA. Its dynamic assembly and disassembly ensure efficient repair of DNA damage while minimizing disruption to the genome.'
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Proteins (4)
| Protein | Definition | Taxonomy |
|---|---|---|
| DNA repair endonuclease XPF | A DNA repair endonuclease XPF that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| DNA repair protein complementing XP-G cells | A DNA excision repair protein ERCC-5 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| DNA polymerase delta catalytic subunit | A DNA polymerase delta catalytic subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:P28340] | Homo sapiens (human) |
| DNA excision repair protein ERCC-1 | A DNA excision repair protein ERCC-1 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
Compounds (11)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| foscarnet | Foscarnet: An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. phosphonoformic acid : Phosphoric acid in which one of the hydroxy groups is replaced by a carboxylic acid group. It is used as the trisodium salt as an antiviral agent in the treatment of cytomegalovirus retinitis (CMV retinitis, an inflamation of the retina that can lead to blindness) and as an alternative to ganciclovir for AIDS patients who require concurrent antiretroviral therapy but are unable to tolerate ganciclovir due to haematological toxicity. | carboxylic acid; one-carbon compound; phosphonic acids | antiviral drug; geroprotector; HIV-1 reverse transcriptase inhibitor; sodium-dependent Pi-transporter inhibitor |
| ochracin | ochracin: produced by Aspergillus alutaceus; structure in first source | isochromanes | |
| zidovudine triphosphate | |||
| n-hydroxynaphthalimide | N-hydroxynaphthalimide: structure in first source | ||
| 3-hydroxy-quinazoline-2,4-dione | 3-hydroxy-quinazoline-2,4-dione: structure in first source | ||
| aphidicolin | aphidicolin : A tetracyclic diterpenoid that has an tetradecahydro-8,11a-methanocyclohepta[a]naphthalene skeleton with two hydroxymethyl substituents at positions 4 and 9, two methyl substituents at positions 4 and 11b and two hydroxy substituents at positions 3 and 9. An antibiotic with antiviral and antimitotical properties. Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication. Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells. | tetracyclic diterpenoid | antimicrobial agent; antimitotic; antineoplastic agent; antiviral drug; apoptosis inducer; Aspergillus metabolite; DNA synthesis inhibitor; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; fungal metabolite |
| pnu183792 | PNU183792: structure in first source | ||
| 4-phenyl-4-oxo-2-hydroxybuten-2-oic acid | 2,4-dioxo-4-phenylbutanoic acid: structure in first source | ||
| pecilocin | pecilocin: fungicidal antibiotic produced by Paecilomyces varioti Bainier var. antibioticus; structure | N-acylpyrrolidine | |
| sch 725680 | Sch 725680: an aazaphilone from Aspergillus sp.; structure in first source | ||
| pinophilin b | pinophilin B: from cultures of a fungus (Penicillium pinophilum Hedgcok) derived from a seaweed; structure in first source |