DNA recombination and repair / edited by Paul J. Smith and Christopher J. Jones.

Format:

Book

Contributor:

Smith, Paul J. (Paul James), 1953-

Jones, Christopher J. (Christopher John), 1965-

Series:

Frontiers in molecular biology ; 22.

Frontiers in molecular biology ; 22

Language:

English

Subjects (All):

DNA repair.

Genetic recombination.

DNA Repair.

Recombination, Genetic.

Medical Subjects:

DNA Repair.

Recombination, Genetic.

Physical Description:

xix, 236 pages : illustrations ; 26 cm.

Place of Publication:

Oxford ; New York : Oxford University Press, 1999.

Summary:

The processes of DNA recombination and repair are vital to cell integrity -- an error can lead to a disease such as cancer. These processes are therefore expanding areas of research and are now being taught in many undergraduate and postgraduate courses. Filling a need for timely and accurate information on the subject, this book studies the cellular processes involved in DNA recombination and repair by highlighting a selection of issues currently at the forefront of understanding. Chapters address genome integrity as it is important to health, and authors include the relevance of DNA repair and recombination to ill health and cancer in particular. As well, molecular pathways of apoptosis induction are clearly referenced whenever necessary. DNA Recombination and Repair will undoubtedly benefit advanced students and professionals and will likely interest anyone intrigued by the processes of DNA.

Contents:

1 Molecular processing of DNA folding anomalies in Escherichia coli / David R. F. Leach 1

2. Folding anomalies in DNA 1

2.1 Hairpin DNA 1

2.2 Pseudo-hairpin DNA and S-DNA 2

2.3 H-DNA, *H-DNA, and nodule DNA 4

2.4 Z-DNA 6

2.5 Quadruplex DNA 6

3. Deletions at direct repeats stimulated by closely spaced inverted repeats 6

4. Duplications and inversions stimulated by closely spaced inverted repeats 8

5. Deletions and amplifications of triplet repeats 9

6. Inhibition of DNA replication and initiation of homologous recombination by SbcCD protein 9

2 Double-strand break repair and V(D)J recombination / Belinda K. Singleton, Penny A. Jeggo 16

2. V(D)J recombination 16

2.1 Recognition and cleavage of the signal sequences 17

2.2 Processing and joining the dsbs 17

3. Mechanisms of DNA double-strand break repair 19

3.1 Homologous recombination 19

3.2 Single-strand annealing 22

3.3 Non-homologous end-joining (NHEJ) 22

4. Identification of the genes involved in NHEJ 25

4.1 DNA-dependent protein kinase, DNA-PK 25

4.2 XRCC4 and DNA ligase IV 26

4.3 Yeast as a model system 27

5. The phenotypes of mammalian mutants defective in NHEJ 27

3 Translesion replication / Christopher Lawrence, Roger Woodgate 38

2. Tranlesion replication in E. coli 40

2.1 Translesion replication is usually a strategy of last resort 40

2.2 Most translesion replication is dependent upon the Umu proteins 41

2.3 Umu-dependent TR is regulated with exquisite precision 42

2.4 Formation of the mutasome and translesion replication 45

2.5 The Umu proteins are generalized elongation factors 47

2.6 Translesion replication in the absence of Umu proteins 48

3. Translesion replication in yeast 50

3.1 Genes important for TR and their mutant phenotypes 50

3.2 Regulation of translesion replication 51

3.3 Molecular and enzymatic analysis of REV gene function 53

4. The mutagenic properties of DNA damage 55

5. Comparisons, speculations, and TR in humans 56

4 Mismatch repair and cancer / P. Karran, M. Bignami 66

2. Bacterial mismatch repair 67

2.1 The identification of bacterial mismatch repair genes 67

2.2 The biochemistry of mismatch repair in Escherichia coli 68

3. Human mismatch repair 69

3.1 Identification of human mismatch repair genes 69

3.2 Microsatellite instability and mutator effects in repair-defective human cells 71

3.3 The biochemistry of the human mismatch repair pathway 78

3.4 An alternative mismatch repair pathway 81

4. Mismatch repair defects in mouse models 82

4.1 Mice as models for HNPCC 84

5. Mismatch repair defects and susceptibility to therapeutic agents 84

6. Important areas for the future 87

6.1 Mismatch repair, transcription-coupled excision repair, and recombinational repair 87

6.2 Adaptive responses and reduced mismatch repair efficiency 88

6.3 Epigenetic effects on mismatch repair genes 88

6.4 Mismatch repair cell-cycle checkpoints and apoptosis 89

5 Enzymology of human nucleotide excision repair / Hanspeter Naegeli 99

2. Human NER factors and general strategies 100

3. The human genetic framework: xeroderma pigmentosum 102

4. The biochemical framework: in vitro reconstitution of human NER activity 103

4.1 XPA 103

4.2 RPA 106

4.3 XPA-HHR23B 107

4.4 TFIIH 108

4.5 XPF-ERCC1 and XPG 110

4.6 RFC, PCNA, DNA Pol [varepsilon], and DNA ligase I 112

5. The substrate-discrimination problem 112

5.1 Heterogeneity of DNA damage recognition 113

5.2 Damaged DNA binding proteins 114

5.3 Shielding from excision repair 116

5.4 The damaged DNA binding function of XPA protein 117

5.5 The role of multiprotein assembly in damage recognition 119

6. Bipartite substrate discrimination in human NER 120

6.1 Analysis of substrate discrimination using C4' backbone modifications 120

6.2 Significance of bipartite recognition in mutagenesis and carcinogenesis 123

6.3 A potential sensor of defective Watson-Crick hybridization 125

6.4 A potential sensor of defective deoxyribonucleotide chemistry 126

6 Transcription-coupled and global genome repair in yeast and humans / Marcel Tijsterman, Richard A. Verhage, Jaap Brouwer 138

2.1 Gene-specific repair analysis 139

2.2 Nucleotide-specific repair analysis 139

2.3 Nucleotide excision repair in vitro 141

3. Transcription-coupled nucleotide excision repair 141

3.1 General features of RNA polymerase II transcription 144

3.2 TFIIH: required for RNA pol II transcription and nucleotide excision repair 145

3.3 Coupling NER to transcription in E. coli: a paradigm for eukaryotes? 146

3.4 Transcription-coupled repair in humans 146

3.5 Transcription-coupled repair in the yeast Saccharomyces cerevisiae 148

3.6 Molecular mechanisms of TCR in eukaryotes 150

4. Global genome nucleotide excision repair 152

4.1 XP-C and repair of non-transcribed DNA 154

4.2 Rad7 and Rad16 and repair of non-transcribed DNA 155

5. Connections between NER and other repair pathways 157

5.1 NER and direct reversal by DNA photolyases 158

5.2 NER and mismatch repair 158

5.3 Nucleotide and base excision repair 158

7 The ATM gene and stress response / Martin F. Lavin, Kum Kum Khanna 166

2. Ataxia-telangiectasia 167

3. Cloning of ATM 169

3.1 Mutation analysis 170

3.2 ATM cDNA 171

3.3 Genomic organization of ATM 172

4. The ATM protein 172

4.1 Detection and importance for radiosensitivity 172

4.2 Cellular localization 173

5. ATM gene family 175

5.1 DNA-dependent protein kinase 176

5.2 Atr (ataxia-telangiectasia and rad3-related) 177

6. Mouse models 178

7. Role of ATM in cell-cycle control 179

7.1 G[subscript 1]/S-phase checkpoint 179

7.2 S-phase and G[subscript 2]/M checkpoints 183

7.3 Cell cycle and radiosensitivity 185

8. Role of ATM in meiosis 186

9. Integrated view of the role of ATM 187

8 p53 and the integrated response to DNA damage / Paul J. Smith, Christopher J. Jones 202

2. DNA damage: induction and processing 202

3. DNA damage induction by anticancer agents 205

3.1 Alkylating agents 205

3.2 Antibiotics: parallels with ionizing radiation 206

3.3 DNA topoisomerase inhibitors 207

4. Cellular responses to stress and the role of p53 209

4.1 p53 and cycle arrest 210

4.2 p53 and nucleotide excision repair 213

5. p53 as a damage sensor in replicative senescence 214

5.1 Replicative senescence and telomeric clocks? 214

5.2 Telomeres: form and function 215

5.3 Telomerase 216

5.4 p53 and replicative senescence 216

5.5 Nature of the p53-activating signal at senescence and the role of DNA repair pathways? 217

6. Human cancer-prone disorders 220

6.1 Perspective 220

6.2 Germline disorders involving dominant proto-oncogenes and dominant tumour suppressor genes 221.

Notes:

Includes bibliographical references and index.

ISBN:

0199637075

0199637067

OCLC:

41503892