background:
This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Naturally-occurring readthrough transcription occurs between this gene and the adjacent PGBD3 gene (GeneID:267004), and results in a fusion protein that shares sequence with the product of each individual gene. The readthrough locus is represented by GeneID:101243544. [provided by RefSeq, Mar 2013]
Function:
Essential factor involved in transcription-coupled nucleotide excision repair which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA. It is required for transcription-coupled repair complex formation. It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the at sites of RNA polymerase II-blocking lesions.
Subcellular Location:
Nucleus.
Post-translational modifications:
Phosphorylated upon DNA damage, probably by ATM or ATR.
Ubiquitinated at the SLCterminus. Ubiquitination by the CSA complex leads to ERCC6 proteasomal degradation in a USLVdependent manner.
DISEASE:
Defects in ERCC6 are the cause of Cockayne syndrome type B (CSB) [MIM:133540]. Cockayne syndrome is a rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.
Defects in ERCC6 are the cause of cerebro-oculo-facio-skeletal syndrome type 1 (COFS1) [MIM:214150]; also known as COFS syndrome or Pena-Shokeir syndrome type 2. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.
Defects in ERCC6 are a cause of De Sanctis-Cacchione syndrome (DSC) [MIM:271760]; also known as xerodermic idiocy. DSC is an autosomal recessive syndrome consisting of xeroderma pigmentosum associated with mental retardation, retarded growth, gonadal hypoplasia and sometimes neurologic complications.
Note=A genetic variation in the 5-prime flanking region of ERCC6 has been shown to be associated with susceptibility to age-related macular degeneration.
Defects in ERCC6 are a cause of USLVsensitive syndrome (UVS) [MIM:600630]. UVS is a rare autosomal recessive disorder characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors.
Similarity:
Belongs to the SNF2/RAD54 helicase family.
Contains 1 helicase ATP-binding domain.
Contains 1 helicase SLCterminal domain.
Database links:
Entrez Gene: 2074 Human
Entrez Gene: 319955 Mouse
Omim: 609413 Human
SwissProt: Q03468 Human
SwissProt: Q5W0L9 Human
SwissProt: Q8C851 Mouse
Unigene: 654449 Human
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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