Biochemistry (Moscow)

, Volume 76, Issue 1, pp 16–23

Multiple DNA damage recognition factors involved in mammalian nucleotide excision repair

Review

DOI: 10.1134/S0006297911010044

Cite this article as:
Sugasawa, K. Biochemistry Moscow (2011) 76: 16. doi:10.1134/S0006297911010044

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.

Key words

nucleotide excision repair DNA damage recognition xeroderma pigmentosum XPC UV-DDB TFIIH 

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

Supplementary material

10541_2011_9355_MOESM1_ESM.pdf (282 kb)
Supplementary material, approximately 282 KB.

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  1. 1.Biosignal Research Center, Organization of Advanced Science and TechnologyKobe UniversityKobe, HyogoJapan

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