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Multiple DNA damage recognition factors involved in mammalian nucleotide excision repair

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Abstract

The nucleotide excision repair (NER) subpathway operating throughout the mammalian genome is a versatile DNA repair system that can remove a wide variety of helix-distorting base lesions. This system contributes to prevention of blockage of DNA replication by the lesions, thereby suppressing mutagenesis and carcinogenesis. Therefore, it is of fundamental significance to understand how the huge genome can be surveyed for occurrence of a small number of lesions. Recent studies have revealed that this difficult task seems to be accomplished through sequential actions of multiple DNA damage recognition factors, including UV-DDB, XPC, and TFIIH. Notably, these factors adopt completely different strategies to recognize DNA damage. XPC detects disruption and/or destabilization of the base pairing, which ensures a broad spectrum of substrate specificity for global genome NER. In contrast, UV-DDB directly recognizes particular types of lesions, such as UV-induced photoproducts, thereby vitally recruiting XPC as well as further extending the substrate specificity. After DNA binding by XPC, moreover, the helicase activity associated with TFIIH scans a DNA strand to make a final search for the presence of aberrant chemical modifications of DNA. The combination of these different strategies makes a crucial contribution to simultaneously achieving efficiency, accuracy, and versatility of the entire repair system.

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Abbreviations

AAF:

N-acetyl-2-aminofluorene

BHD:

β-hairpin domain

CPDs:

cyclobutane pyrimidine dimers

CS:

Cockayne syndrome

NER:

nucleotide excision repair

PCNA:

proliferating cell nuclear antigen

6-4PPs:

pyrimidine-pyrimidone (6-4) photoproducts

RFC:

replication factor C

RPA:

replication protein A

TGD:

transglutaminase-homology domain

TTD:

trichothiodystrophy

UV-DDB:

UV-damaged DNA-binding protein consisting of two subunits (DDB1 and DDB2)

XP:

xeroderma pigmentosum

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  1. Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, Hyogo, 657-8501, Japan

    K. Sugasawa

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Published in Russian in Biokhimiya, 2011, Vol. 76, No. 1, pp. 22–31.

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Sugasawa, K. Multiple DNA damage recognition factors involved in mammalian nucleotide excision repair. Biochemistry Moscow 76, 16–23 (2011). https://doi.org/10.1134/S0006297911010044

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