DNA DAMAGE RECOGNITION
CONTENTS PART I MECHANISMS OF DAMAGE RECOGNITION: THEORETICAL CONSIDERATIONS 1 DYNAMICS OF DNA DAMAGE RECOGNITION 1 INTRODUCTION 2 ROLE OF DNA FLEXIBILITY IN SEQUENCE-DEPENDENT ACTIVITY OF UDG 3 OPENING AND BENDING DYNAMICS OF GU MISMATCHES IN DNA 4 CONCLUSIONS REFERENCES 2 IN SEARCH OF DAMAGED BASES 2 MECHANISM FOR AN INCREASED RATE OF TARGET SITE LOCATION 3 IN VITRO EVIDENCE FOR PROCESSIVE NICKING ACTIVITY OF DNA GLYCOSYLASES 4 DISCOVERY AND SIGNI?CANCE OF IN VIVO PROCESSIVE NICKING ACTIVITY BY T4-PDG 5 DNA BENDING AS A POTENTIAL PREREQUISITE FOR NUCLEOTIDE FLIPPING 6 MECHANISMS OF NUCLEOTIDE FLIPPING 7 SPECI?CITY OF GLYCOSYLASE BINDING SITES AND CATALYTIC ACTIVITIES 3 INCREASED SPECI?CITY AND EF?CIENCY OF BASE EXCISION REPAIR THROUGH COMPLEX FORMATION 2 DNA LESION RECOGNITION AND REMOVAL 3 STRAND INCISION 4 GAP FILLING AND RELIGATION 5 XRCC1 COORDINATION 6 LONG-PATCH REPAIR 7 EMERGING SUBPATHWAYS 8 CONCLUSIONS PART II UV DAMAGE AND OTHER BULKY DNA-ADDUCTS 4 STRUCTURE AND PROPERTIES OF DNA PHOTOPRODUCTS 2 CYCLOBUTANE PYRIMIDINE DIMERS 3 OTHER DIMER-RELATED PRODUCTS 4 (6–4) PRODUCTS 5 DEWAR PHOTOPRODUCT 6 SPORE PHOTOPRODUCT 7 TA PRODUCT 5 DAMAGE RECOGNITION BY DNA PHOTOLYASES 1 OVERVIEW OF PHOTOLYASES 2 THE NATURE OF THE SUBSTRATES 3 CHARACTERIZATION OF SUBSTRATE BINDING AND DISCRIMINATION BY PHOTOLYASES 4 INTERACTIONS AT THE PHOTOLYASE–PHOTOPRODUCT INTERFACE: THE MOLECULAR BASIS FOR SUBSTRATE BINDING AND DISCRIMINATION 5 SUBSTRATE BINDING IN VIVO 6 SUMMARY AND FUTURE DIRECTIONS 6 DAMAGE RECOGNITION BY THE BACTERIAL NUCLEOTIDE EXCISION REPAIR MACHINERY 2 DIVERSITY OF DNA LESIONS RECOGNIZED 3 THE PROTEINS AND THEIR STRUCTURAL DOMAINS 4 REACTION PATHWAY FOR DAMAGE DETECTION AND PROCESSING 5 DNA DAMAGE RECOGNITION WITHIN THE BIOLOGICAL CONTEXT OF THE CELL 6 SIMILARITIES IN DAMAGE RECOGNITION AND VERI?CATION BETWEEN BACTERIAL AND EUKARYOTIC NUCLEOTIDE EXCISION REPAIR SYSTEMS 7 RECOGNITION OF DNA DAMAGE DURING EUKARYOTIC NUCLEOTIDE EXCISION REPAIR 2 NUCLEOTIDE EXCISION REPAIR SUBSTRATES 3 EUKARYOTIC NER REACTION 4 SUBUNITS OF THE EUKARYOTIC NER MACHINERY 5 STEPWISE ASSEMBLY OF THE MAMMALIAN NER RECOGNITION COMPLEX 6 A PREASSEMBLED REPAIROSOME IN YEAST? 7 ROLE OF DAMAGED DNA BINDING IN DAMAGE RECOGNITION 8 RECOGNITION OF BULKY LESIONS DURING TRANSCRIPTION-COUPLED DNA REPAIR 9 BIPARTITE SUBSTRATE DISCRIMINATION IN THE GGR PATHWAY 10 XPC–HHR23B AS A SENSOR OF DEFECTIVE BASE PAIRING 11 TRANSCRIPTION FACTOR IIH AS A SENSOR OF DEFECTIVE DEOXYRIBONUCLEOTIDE CHEMISTRY 12 ROLE OF XPA–RPA IN INTEGRATING DIFFERENT RECOGNITION SIGNALS 13 DAMAGE-SPECI?C RECRUITMENT OF XPG AND XPF–ERCC1 14 REGULATION OF THE DAMAGE RECOGNITION PROCESS 15 CONCLUSIONS 8 INTERACTIONS OF THE TRANSCRIPTION MACHINERY WITH DNA DAMAGE IN PROKARYOTES 1 GENERAL OVERVIEW 2 THE BEHAVIOR OF RNA POLYMERASE COMPLEXES WITH DIFFERENT TYPES OF DNA DAMAGE 3 THE BEHAVIOR OF RNA POLYMERASE COMPLEXES AT LESIONS AND NER 4 THE BEHAVIOR OF RNA POLYMERASE COMPLEXES AT LESIONS AND BER 5 SUMMARY AND FUTURE DIRECTIONS 9 DNA REPAIR IN ACTIVELY TRANSCRIBED GENES IN EUKARYOTIC CELLS 2 HETEROGENEITY OF DNA REPAIR 3 METHODS FOR DETECTING TCR AND GGR 4 DNA REPAIR IN TRANSCRIPTIONALLY ACTIVE GENES IN DIFFERENT ORGANISMS 5 MODELS OF TCR IN EUKARYOTIC CELLS 6 EFFECT OF DIFFERENT KINDS OF DNA DAMAGE ON TCR 10 CHROMATIN STRUCTURE AND THE REPAIR OF UV LIGHT-INDUCED DNA DAMAGE 2 NUCLEOSOMES: HETEROGENEITY IN A CONSERVED STRUCTURE 3 DYNAMIC PROPERTIES OF NUCLEOSOMES REGULATE DNA ACCESSIBILITY 4 DAMAGE TOLERANCE OF NUCLEOSOMES 5 REPAIR OF NUCLEOSOMES BY PHOTOLYASE 6 REPAIR OF NUCLEOSOMES BY NER 7 SITE-SPECI?C REPAIR IN NUCLEOSOME AND DAMAGE RECOGNITION 8 CHROMATIN REMODELING AND DNA REPAIR 9 CONCLUSIONS 11 THE ULTRAVIOLET DAMAGE ENDONUCLEASE (UVDE) PROTEIN AND ALTERNATIVE EXCISION REPAIR: A HIGHLY DIVERSE SYSTEM FOR DAMAGE RECOGNITION AND PROCESSING 2 DISCOVERY AND INITIAL CHARACTERIZATION OF S POMBE UVDE 3 RECOGNITION AND PROCESSING OF UV PHOTOPRODUCTS 4 RECOGNITION AND PROCESSING OF PLATINUM G-G DIADDUCTS 5 RECOGNITION AND PROCESSING OF ABASIC SITES 6 MODI?ED BASES NOT RECOGNIZED BY UVDE 7 RECOGNITION AND PROCESSING OF BASE–BASE MISMATCHES 8 RECOGNITION AND PROCESSING OF INSERTION–DELETION LOOPS 9 SUBSEQUENT STEPS FOLLOWING UVDE-INITIATED ALTERNATIVE EXCISION REPAIR 10 SCHIZOSACCHAROMYCES POMBE UVDE HOMOLOGS 11 CONCLUSIONS 12 STRUCTURAL ASPECTS OF PT-DNA ADDUCT RECOGNITION BY PROTEINS 1 BACKGROUND 2 INTRODUCTION 3 STRUCTURAL CONSEQUENCES OF PLATINUM-BINDING TO DOUBLE-STRANDED DNA 4 RECOGNITION OF CIS-DDP-1,2 INTRASTRAND CROSS-LINK BY CELLULAR PROTEINS 5 SUMMARY AND OUTLOOK 13 STRUCTURAL ASPECTS OF POLYCYCLIC AROMATIC CARCINOGEN-DAMAGED DNA AND ITS RECOGNITION BY NER PROTEINS 2 METABOLISM OF PAH TO DIOL EPOXIDES AND FORMATION OF STEREOISOMERIC DNA ADDUCTS 3 METHODS 4 PAH–DNA ADDUCTS: CONFORMATIONAL MOTIFS 5 INSIGHTS INTO THE STRUCTURAL MOTIFS AT THE NUCLEOSIDE ADDUCT LEVEL DERIVED FROM COMPUTATIONAL APPROACHES 6 PAH–DNA ADDUCT CONFORMATIONAL MOTIFS AND NER 7 STRUCTURAL DIFFERENCES BETWEEN BAY AND FJORD STEREOISOMERIC PAH-N6–ADENINE ADDUCTS AND CORRELATIONS WITH NER SUSCEPTIBILITIES 8 COMPUTATIONAL ANALYSIS PART III NON-BULKY BASE DAMAGE 14 STRUCTURAL FEATURES OF DNA GLYCOSYLASES AND AP ENDONUCLEASES 1 THE BASE EXCISION REPAIR PATHWAY 2 DNA GLYCOSYLASE STRUCTURAL FAMILIES 3 SPECI?C MECHANISMS FOR RECOGNITION OF DAMAGE 4 AP ENDONUCLEASES 5 EMERGING QUESTIONS 15 REPAIR OF OXIDIZED BASES 1 BIOLOGICAL CONSEQUENCES OF OXIDATIVE DAMAGE 2 MAJOR REPAIR ENZYMES THAT RECOGNIZE OXIDATIVE BASE DAMAGE 3 REPAIR PATHWAYS FOR OXIDATIVE DNA DAMAGE 16 RECOGNITION OF ALKYLATING AGENT DAMAGE IN DNA 1 MODI?CATION OF DNA BY SMALL ALKYLATING AGENTS 2 DNA REPAIR SYSTEMS FOR REMOVAL OF ALKYLATING AGENT DAMAGE 3 O6-ALKYLGUANINE DNA METHYLTRANSFERASES—AGTS 4 ALKB—2-OXOGLUTARATE-DEPENDENT FE(II)-DEPENDENT OXYGENASES 5 DNA GLYCOSYLASES—BASE EXCISION REPAIR 6 NUCLEOTIDE EXCISION REPAIR 17 DEAMINATED BASES IN DNA 2 LESIONS AND THEIR CONSEQUENCES 3 DEAMINATING AGENTS 4 ENDONUCLEASE V, AN ENZYME SPECI?C FOR DEAMINATED PURINES 5 HYPOXANTHINE/ALKYLPURINE DNA GLYCOSYLASES 6 ENDONUCLEASE VIII OF E COLI 7 CONCLUSIONS 18 NEW PARADIGMS FOR DNA BASE EXCISION REPAIR IN MAMMALS 2 OXIDIZED BASE-SPECI?C GLYCOSYLASES IN E COLI AND MAMMALS 3 CONCLUSIONS