XPA ( xeroderma pigmentosum , complementation group A )
نویسندگان
چکیده
Initiates DNA repair by binding to damaged sites with various affinities, depending upon the chemical structure of the lesion. Two proteins have been identified and implicated in (one of) the first steps of Nucleotide Excision Repair (NER), i.e. the recognition of lesions in the DNA: the XPA gene product and the XPC gene product. Cells from XPA patients are extremely sensitive to UV and have very low nucleotide excision repair activity. In vitro the XPA protein binds preferentially to damaged DNA compared to nondamaged DNA. The XPA protein binds to replication protein A (RPA) which enhances the affinity of XPA for damaged DNA and is essential for NER. The XPA protein has been shown to bind to ERCC1 and TFIIH. It is possible that the complex XPA/RPA may tell to the repair machinery which strand contained the damage and therefore should be eliminated.
منابع مشابه
A truncated human xeroderma pigmentosum complementation group A protein expressed from an adenovirus sensitizes human tumor cells to ultraviolet light and cisplatin.
Individuals with the genetic disease xeroderma pigmentosum (XP) have impaired nucleotide excision repair (NER). Group A XP cells are defective in the XPA protein essential for NER and serve, together with other NER proteins, as a nucleation factor for the demarcation of bulky DNA damage. Because XPA cells are extremely sensitive to UV and drugs that cause bulky DNA damage, the XPA protein is an...
متن کاملFormation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins.
The xeroderma pigmentosum complementation group A (XP-A) protein, XPA, has recently been expressed in Escherichia coli in a soluble and fully functional form. An affinity column was prepared by linking the XPA protein to a solid support. When HeLa cell-free extract capable of excision repair was applied to the column, > 99.9% of the proteins were in the flow-through. However, the flow-through f...
متن کاملCorrection of the ultraviolet light induced DNA-repair defect in xeroderma pigmentosum cells by electroporation of a normal human endonuclease.
Cells from patients with xeroderma pigmentosum, complementation group A (XPA), are known to be defective in repair of pyrimidine dimers and other forms of damage produced by 254-nm ultraviolet (UVC) radiation. We have isolated a DNA endonuclease, pI 7.6, from the chromatin of normal human lymphoblastoid cells which recognizes damage produced by UVC light, and have introduced this endonuclease i...
متن کاملXPA A23G polymorphism is associated with the elevated response to platinum-based chemotherapy in advanced non-small cell lung cancer.
DNA repair capacity (DRC) is correlated with sensitivity of cancer cells toward platinum-based chemotherapy. We hypothesize that genetic polymorphisms in DNA repair gene XPA (xeroderma pigmentosum group A) and XPG (xeroderma pigmentosum group G) (ERCC5, excision repair cross-complementation group 5), which result in inter-individual differences in DNA repair efficiency, may predict clinical res...
متن کاملPterygium and genetic polymorphisms of the DNA repair enzymes XRCC1, XPA, and XPD
PURPOSE Pterygium is an ultraviolet (UV) related disease. UV radiation can produce DNA damage, which is repaired by the DNA repair systems. Among the DNA repair systems, the base excision repair (BER) and nucleotide excision repair (NER) systems are the major ones involved in repairing UV-induced DNA damage; X-ray repair cross complementary 1 (XRCC1) and human 8-oxoguanine DNA glycosylase 1 (hO...
متن کاملMouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes.
The accumulation of DNA damage is a slow but hazardous phenomenon that may lead to cell death, accelerated aging, and cancer. One of the most versatile defense mechanisms against the accumulation of DNA damage is nucleotide excision repair, in which, among others, the Xeroderma pigmentosum group C (XPC) and group A (XPA) proteins are involved. To elucidate differences in the functions of these ...
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