DNA excision repair protein ERCC-8 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, res ...
that in humans is encoded by the ''ERCC8''
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 b ...
.
This gene encodes a WD repeat protein, which interacts with the
Cockayne syndrome type B
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 ...
(CSB) and
p44 proteins, the latter being a subunit of the RNA polymerase II
transcription factor II H
Transcription factor II Human (transcription factor II H; TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 ...
. Mutations in this gene have been identified in patients with the hereditary disease
Cockayne syndrome (CS). CS is an accelerated aging disorder characterized by
photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicit ...
, impaired development and multi-system progressive degeneration. The CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Multiple alternatively
spliced transcript variants encoding different isoforms have been found for this gene.
CS arises from
germline 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 replication, DNA or viral repl ...
s in either of two
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 b ...
s ''CSA(ERCC8)'' or ''CSB(
ERCC6
DNA excision repair protein ERCC-6 (also CS-B protein) is a protein that in humans is encoded by the ''ERCC6'' gene. The ''ERCC6'' gene is located on the long arm of chromosome 10 at position 11.23.NIH. "ERCC6 Gene." Genetics Home Reference. Natio ...
)''. ''CSA'' mutations generally give rise to a more moderate form of CS than ''CSB'' mutations.
Mutations in the ''CSA'' gene account for about 20% of CS cases.
Function
CSA and CSB proteins are thought to function in
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
and
DNA repair
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 ...
, most notably in transcription-coupled nucleotide excision repair. CSA and CSB-deficient cells exhibit a lack of preferential repair of UV-induced
cyclobutane pyrimidine dimers in actively transcribed genes, consistent with a failed transcription coupled nucleotide excision repair response.
Within the cell, the CSA protein localizes to sites of
DNA damage
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 d ...
, particularly
inter-strand cross-links, double-strand breaks and some mono-adducts.
Interactions
ERCC8 (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
XAB2
Pre-mRNA-splicing factor SYF1 is a protein that in humans is encoded by the ''XAB2'' gene.
Interactions
XAB2 has been shown to interact with ERCC8
DNA excision repair protein ERCC-8 is a protein that in humans is encoded by the ''ERCC8'' ge ...
.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Cockayne syndrome
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