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XPC
Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity. The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1. Belongs to the XPC family. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
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| Protein type: DNA repair, damage |
| Chromosomal Location of mouse Ortholog: 6|6 D1 |
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Cellular Component:
chromosome; cytoplasm; cytosol; intracellular membrane-bounded organelle; mitochondrion; nucleolus; nucleoplasm; nucleotide-excision repair complex; nucleotide-excision repair factor 2 complex; nucleus; plasma membrane; site of DNA damage; XPC complex
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Molecular Function:
damaged DNA binding; DNA binding; DNA damage sensor activity; protein binding; protein-containing complex binding; RNA polymerase II-specific DNA-binding transcription factor binding; single-stranded DNA binding; transcription coactivator activity
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Biological Process:
DNA damage response; DNA repair; mismatch repair; mitotic intra-S DNA damage checkpoint signaling; nucleotide-excision repair; positive regulation of DNA-templated transcription; pyrimidine dimer repair by nucleotide-excision repair; regulation of mitotic cell cycle phase transition; response to UV-B; UV-damage excision repair
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Reference #:
P51612
(UniProtKB)
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Alt. Names/Synonyms: DNA repair protein complementing XP-C cells homolog; OTTMUSP00000028684; p125; Xeroderma pigmentosum group C-complementing protein homolog; xeroderma pigmentosum, complementation group C; Xpc
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Gene Symbols: Xpc
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Molecular weight:
104,522 Da
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Basal Isoelectric point:
8.99
Predict pI for various phosphorylation states
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