DNA repair protein complementing XP-G cells is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''ERCC5''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
Excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G) is involved in excision repair of UV-induced DNA damage. Mutations cause Cockayne syndrome, which is characterized by severe growth defects, mental retardation, and cachexia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been described, but the biological validity of all variants has not been determined.
Mutations in ERCC5 cause
arthrogryposis Arthrogryposis (AMC) describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning 'curving of joints' (', 'joint'; ', late Latin form of late Greek ', 'hooking').
Children born with one ...
.
XPG is a structure specific
endonuclease
In molecular biology, endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain (namely DNA or RNA). Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (with regard to sequence), while man ...
that incises
DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
at the 3’ side of the damaged nucleotide during
nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. Intercalation (biochemistry), intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single ...
.
Syndromes
Mutational defects in the ''Ercc5''(''Xpg'') gene can cause either the cancer-prone condition
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 su ...
(XP) alone, or in combination with the severe neurodevelopmental disorder
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 ( photo ...
(CS) or the infantile lethal cerebro-oculo-facio-skeletal syndrome.
Mouse model
An ''Ercc5''(''Xpg'') mutant mouse model presented features of premature aging including
cachexia
Cachexia () is a syndrome that happens when people have certain illnesses, causing muscle loss that cannot be fully reversed with improved nutrition. It is most common in diseases like cancer, Heart failure, congestive heart failure, chronic o ...
and
osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk.
It is the most common reason f ...
with pronounced degenerative phenotypes in both liver and brain.
These mutant mice developed a multi-system premature aging degenerative phenotype that appears to strengthen the link between
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. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...
and
aging
Ageing (or aging in American English) is the process of becoming Old age, older until death. The term refers mainly to humans, many other animals, and fungi; whereas for example, bacteria, perennial plants and some simple animals are potentiall ...
.
(see
DNA damage theory of aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of DNA damage (naturally occurring), naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although ...
).
Dietary restriction, which extends lifespan of wild-type mice, also substantially increased the lifespan of ''Ercc5''(''Xpg'') mutant mice.
Dietary restriction of the mutant mice, while delaying aging, also appeared to slow the accumulation of genome wide DNA damage and to preserve transcriptional output, thus contributing to improved cell viability.
Interactions
ERCC5 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
ERCC2.
References
External links
GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
External links
{{DNA repair
Human proteins
Oncogenes