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Nucleotide excision repair is a DNA repair mechanism. [2] 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: Nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR).
Nucleotide excision repair (NER) is the primary DNA repair mechanism that removes the therapeutic platinum-DNA adducts from the tumor DNA. ERCC1 activity levels, being an important part of the NER common final pathway, may serve as a marker of general NER throughput.
During nucleotide excision repair, several protein complexes cooperate to recognize damaged DNA and locally separate the DNA helix for a short distance on either side of the site of a site of DNA damage. The ERCC1–XPF nuclease incises the damaged DNA strand on the 5′ side of the lesion. [14]
Excision endonuclease, also known as excinuclease or UV-specific endonuclease, is a nuclease (enzyme) which excises a fragment of nucleotides during DNA repair. The excinuclease cuts out a fragment by hydrolyzing two phosphodiester bonds , one on either side of the lesion in the DNA.
UvrABC endonuclease is a multienzyme complex in bacteria involved in DNA repair by nucleotide excision repair, and it is, therefore, sometimes called an excinuclease.This UvrABC repair process, sometimes called the short-patch process, involves the removal of twelve nucleotides where a genetic mutation has occurred followed by a DNA polymerase, replacing these aberrant nucleotides with the ...
XPC, upon ubiquitination, is activated and initiates the nucleotide excision repair pathway. Somewhat later, at 30 minutes after UV damage, the INO80 chromatin remodeling complex is recruited to the site of the DNA damage, and this coincides with the binding of further nucleotide excision repair proteins, including ERCC1. [67]
The XRCC1 protein does not have enzymatic activity, but acts as a scaffolding protein that interacts with multiple repair enzymes. The scaffolding allows these repair enzymes to then carry out their enzymatic steps in repairing DNA. XRCC1 is involved in single-strand break repair, base excision repair and nucleotide excision repair. [6]
Nucleotide excision repair is one of the main mechanisms used to remove bulky adducts from DNA lesions caused by chemotherapy drugs, environmental mutagens, and most importantly UV radiation. [9] This mechanism functions by releasing a short damage containing oligonucleotide from the DNA site, and then that gap is filled in and repaired by NER. [9]