Xeroderma pigmentosum, complementation group C, also known as XPC, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
which in humans is encoded by the ''XPC''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. XPC is involved in the recognition of bulky DNA adducts in
nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucle ...
.
It is located on chromosome 3.
Function
This gene encodes a component of the
nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucle ...
(NER) pathway. There are multiple components involved in the NER pathway, including
Xeroderma pigmentosum
Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun- ...
(XP) A-G and V,
Cockayne syndrome
Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosen ...
(CS) A and B, and
trichothiodystrophy
Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into ''tricho'' – "hair", '' thio'' – "sulphur", and ''dystrophy'' – "wasting away" or lit ...
(TTD) group A, etc. This component, XPC, plays an important role in the early steps of global genome NER, especially in damage recognition, open complex formation, and repair protein complex formation.
The complex of XPC-RAD23B is the initial damage recognition factor in
global genomic nucleotide excision repair (GG-NER).
XPC-RAD23B recognizes a wide variety of lesions that thermodynamically destabilize DNA duplexes, including UV-induced photoproducts (cyclopyrimidine dimers and 6-4 photoproducts ), adducts formed by environmental mutagens such as benzo
yrene or various aromatic amines, certain oxidative endogenous lesions such as cyclopurines and adducts formed by cancer chemotherapeutic drugs such as cisplatin. The presence of XPC-RAD23B is required for assembly of the other core
NER NER may refer to:
* New European Recordings, a record label
* ISO 3166-1 three letter code for Niger
* Named entity recognition, a text processing task that identifies certain words as belonging to one class or another
* Northeast Regional, an Amt ...
factors and progression through the NER pathway both in vitro and in vivo.
Although most studies have been performed with XPC-RAD23B, it is part of a trimeric complex with centrin-2, a calcium-binding protein of the calmodulin family.
Clinical significance
Mutations in this gene or some other NER components result in
Xeroderma pigmentosum
Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun- ...
, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age.
Cancer
DNA damage appears to be the primary underlying cause of cancer,
and deficiencies in DNA repair genes likely underlie many forms of cancer.
If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s due to error-prone
translesion synthesis
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
. Excess DNA damage may also increase
epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
alterations due to errors during DNA repair.
Such mutations and epigenetic alterations may give rise to
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
.
Reductions in expression of DNA repair genes (usually caused by epigenetic alterations such as promoter hypermethylation) are very common in cancers, and are ordinarily much more frequent than mutational defects in DNA repair genes in cancers. The table below shows that XPC expression was frequently epigenetically reduced in bladder cancer and also in non-small cell lung cancer, and also shows that XPC was more frequently reduced in the more advanced stages of these cancers.
While epigenetic hypermethylation of the promoter region of the ''XPC'' gene was shown to be associated with low expression of XPC,
another mode of epigenetic repression of ''XPC'' may also occur by over-expression of the
microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
miR-890.
Interactions
XPC (gene) has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
ABCA1
ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the ''cholesterol efflux regulatory protein'' (CERP) is a protein which in humans is encoded by the ''ABCA1'' gene. This transporter is a major ...
,
CETN2
Centrin-2 is a protein that in humans is encoded by the ''CETN2'' gene. It belongs to the centrin family of proteins.
Centrin-2 belongs to a family of calcium-binding proteins and is a structural component of the centrosome. The high level of co ...
and
XPB
XPB (xeroderma pigmentosum type B) is an ATP-dependent DNA helicase in humans that is a part of the TFIIH transcription factor complex.
Structure
The 3D-structure of the archaeal homolog of XPB has been solved by X-ray crystallography by Dr. Jo ...
.
References
Further reading
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External links
GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
{{DNA repair