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Nucleotide Excision Repair in Higher Eukaryotes: Mechanism of Primary Damage Recognition in Global Genome Repair

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Genome Stability and Human Diseases

Part of the book series: Subcellular Biochemistry ((SCBI,volume 50))

Abstract

Nucleotide excision repair (NER) is one of the major DNA repair pathways in eukaryotic cells that counteract the formation of genetic damage. NER removes structurally diverse lesions such as pyrimidine dimers, arising upon UV irradiation, and bulky chemical adducts, arising upon exposure to carcinogens and some chemotherapeutic drugs. NER defects lead to severe diseases, including some forms of cancer. In view of the broad substrate specificity of NER, it is of interest to understand how a certain set of proteins recognizes various DNA lesions in the contest of a large excess of intact DNA. This review focuses on DNA damage recognition, the key and, as yet, most questionable step of NER. Understanding of mechanism of this step of NER may give a key contribution to study of similar processes of DNA damage recognition (base excision repair, mismatch repair) and regulation of assembly of various DNA repair machines. The major models of primary damage recognition and pre-incision complex assembly are considered. The model of a sequential loading of repair proteins on damaged DNA seems most reasonable in the light of the available data. The possible contribution of affinity labeling technique in study of this process is discussed.

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Abbreviations

AAF:

acetylaminofluorene

Antr:

anthracene

BER:

base excision repair

BHD:

beta-hairpin domain

CPD:

cyclobutane pyrimidine dimers

DBD:

DNA binding domain

dsDNA:

double-stranded DNA

ERCC1:

excision repair cross-complementing rodent repair deficiency, complementation group 1

FAP-dCTP:

exo-N-[2-N-(N-(4-azido-2,5-difluoro-3-chloropyridine-6-yl)-3-aminopropionyl)-aminoethyl]-deoxycytidine-triphosphate

FAP-dUTP:

5-{N-[N-(4-azido-2,5-difluoro-3 chloropyridine-6-yl)-3-aminopropionyl]-trans-3-aminopropenyl-1}-deoxyuridine-triphosphate

FAP:

fluoro-arylazido

Flu:

fluoresceinyl

CS:

Cockayne syndrome

GFP:

green fluorescent protein

GG-NER:

global genome repair

NER:

nucleotide excision repair

PCNA:

poliferating cell nuclear antigen

RPA:

replication protein A

ssDNA:

single-stranded DNA

TFIIH:

transcription factor IIH

TTD:

tichothiodistrophy

UbL:

ubiquitin-like

UV-DDB:

UV-damaged DNA-binding protein

UvrABC:

UV resistant protein ABC

XP:

xeroderma pigmentosum

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Acknowledgments

This work was supported by the Russian Foundation for Basic Research (project nos. 08-04-91202, 09-04-00479), INTAS-SBRAS (grant no. 06-1000013-9210), and by grants from program “Leading Scientific Schools” (652.2008) and RAS program on Molecular and Cellular Biology.

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  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    N.I. Rechkunova & O.I. Lavrik

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    Heinz-Peter Nasheuer

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Rechkunova, N., Lavrik, O. (2010). Nucleotide Excision Repair in Higher Eukaryotes: Mechanism of Primary Damage Recognition in Global Genome Repair. In: Nasheuer, HP. (eds) Genome Stability and Human Diseases. Subcellular Biochemistry, vol 50. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3471-7_13

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