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DNA Recombination and Repair : Frontiers in Molecular Biology - Paul J. Smith

DNA Recombination and Repair

Frontiers in Molecular Biology

By: Paul J. Smith (Editor), Christopher Jones (Editor)

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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.

"An overview of current knowledge on DNA recombination and repair. Topics covered include DNA structure and folding dynamics, features of recognition and cleavage of signal sequences impact upon double strand break repair, strategies for dealing with DNA mismatches or lesions, the enzymology of
excision repair, and the integration of DNA repair into other cellular pathways."--SciTech Book News

List of contributorsp. xv
Abbreviationsp. xvii
Molecular processing of DNA folding anomalies in Escherichia colip. 1
Introductionp. 1
Folding anomalies in DNAp. 1
Hairpin DNAp. 1
Pseudo-hairpin DNA and S-DNAp. 2
H-DNA, *H-DNA, and nodule DNAp. 4
Z-DNAp. 6
Quadruplex DNAp. 6
Deletions at direct repeats stimulated by closely spaced inverted repeatsp. 6
Duplications and inversions stimulated by closely spaced inverted repeatsp. 8
Deletions and amplifications of triplet repeatsp. 9
Inhibition of DNA replication and initiation of homologous recombination by SbcCD proteinp. 9
Conclusionsp. 10
Acknowledgementsp. 11
Referencesp. 12
Double-strand break repair and V(D)J recombinationp. 16
Introductionp. 16
V(D)J recombinationp. 16
Recognition and cleavage of the signal sequencesp. 17
Processing and joining the dsbsp. 17
Mechanisms of DNA double-strand break repairp. 19
Homologous recombinationp. 19
Single-strand annealingp. 22
Non-homologous end-joining (NHEJ)p. 22
Identification of the genes involved in NHEJp. 25
DNA-dependent protein kinase, DNA-PKp. 25
XRCC4 and DNA ligase IVp. 26
Yeast as a model systemp. 27
The phenotypes of mammalian mutants defective in NHEJp. 27
Conclusionsp. 30
Referencesp. 31
Translesion replicationp. 38
Introductionp. 38
Tranlesion replication in E. colip. 40
Translesion replication is usually a strategy of last resortp. 40
Most translesion replication is dependent upon the Umu proteinsp. 41
Umu-dependent TR is regulated with exquisite precisionp. 42
Formation of the mutasome and translesion replicationp. 45
The Umu proteins are generalized elongation factorsp. 47
Translesion replication in the absence of Umu proteinsp. 48
Translesion replication in yeastp. 50
Genes important for TR and their mutant phenotypesp. 50
Regulation of translesion replicationp. 51
Molecular and enzymatic analysis of REV gene functionp. 53
The mutagenic properties of DNA damagep. 55
Comparisons, speculations, and TR in humansp. 56
Referencesp. 58
Mismatch repair and cancerp. 66
Introductionp. 66
Bacterial mismatch repairp. 67
The identification of bacterial mismatch repair genesp. 67
The biochemistry of mismatch repair in Escherichia colip. 68
Human mismatch repairp. 69
Identification of human mismatch repair genesp. 69
Microsatellite instability and mutator effects in repair-defective human cellsp. 71
The biochemistry of the human mismatch repair pathwayp. 78
An alternative mismatch repair pathwayp. 81
Mismatch repair defects in mouse modelsp. 82
Mice as models for HNPCCp. 84
Mismatch repair defects and susceptibility to therapeutic agentsp. 84
Important areas for the futurep. 87
Mismatch repair, transcription-coupled excision repair, and recombinational repairp. 87
Adaptive responses and reduced mismatch repair efficiencyp. 88
Epigenetic effects on mismatch repair genesp. 88
Mismatch repair cell-cycle checkpoints and apoptosisp. 89
Referencesp. 90
Enzymology of human nucleotide excision repairp. 99
Introductionp. 99
Human NER factors and general strategiesp. 100
The human genetic framework: xeroderma pigmentosump. 102
The biochemical framework: in vitro reconstitution of human NER activityp. 103
XPAp. 103
RPAp. 106
XPA-HHR23Bp. 107
TFIIHp. 108
XPF-ERCC1 and XPGp. 110
RFC, PCNA, DNA Pol [varepsilon], and DNA ligase Ip. 112
The substrate-discrimination problemp. 112
Heterogeneity of DNA damage recognitionp. 113
Damaged DNA binding proteinsp. 114
Shielding from excision repairp. 116
The damaged DNA binding function of XPA proteinp. 117
The role of multiprotein assembly in damage recognitionp. 119
Bipartite substrate discrimination in human NERp. 120
Analysis of substrate discrimination using C4' backbone modificationsp. 120
Significance of bipartite recognition in mutagenesis and carcinogenesisp. 123
A potential sensor of defective Watson-Crick hybridizationp. 125
A potential sensor of defective deoxyribonucleotide chemistryp. 126
Conclusionsp. 128
Acknowledgementsp. 129
Referencesp. 129
Transcription-coupled and global genome repair in yeast and humansp. 138
Introductionp. 138
Techniquesp. 139
Gene-specific repair analysisp. 139
Nucleotide-specific repair analysisp. 139
Nucleotide excision repair in vitrop. 141
Transcription-coupled nucleotide excision repairp. 141
General features of RNA polymerase II transcriptionp. 144
TFIIH: required for RNA pol II transcription and nucleotide excision repairp. 145
Coupling NER to transcription in E. coli: a paradigm for eukaryotes?p. 146
Transcription-coupled repair in humansp. 146
Transcription-coupled repair in the yeast Saccharomyces cerevisiaep. 148
Molecular mechanisms of TCR in eukaryotesp. 150
Global genome nucleotide excision repairp. 152
XP-C and repair of non-transcribed DNAp. 154
Rad7 and Rad16 and repair of non-transcribed DNAp. 155
Connections between NER and other repair pathwaysp. 157
NER and direct reversal by DNA photolyasesp. 158
NER and mismatch repairp. 158
Nucleotide and base excision repairp. 158
Acknowledgementsp. 159
Referencesp. 159
The ATM gene and stress responsep. 166
Introductionp. 166
Ataxia-telangiectasiap. 167
Cloning of ATMp. 169
Mutation analysisp. 170
ATM cDNAp. 171
Genomic organization of ATMp. 172
The ATM proteinp. 172
Detection and importance for radiosensitivityp. 172
Cellular localizationp. 173
ATM gene familyp. 175
DNA-dependent protein kinasep. 176
Atr (ataxia-telangiectasia and rad3-related)p. 177
Mouse modelsp. 178
Role of ATM in cell-cycle controlp. 179
G[subscript 1]/S-phase checkpointp. 179
S-phase and G[subscript 2]/M checkpointsp. 183
Cell cycle and radiosensitivityp. 185
Role of ATM in meiosisp. 186
Integrated view of the role of ATMp. 187
Referencesp. 190
p53 and the integrated response to DNA damagep. 202
Introductionp. 202
DNA damage: induction and processingp. 202
DNA damage induction by anticancer agentsp. 205
Alkylating agentsp. 205
Antibiotics: parallels with ionizing radiationp. 206
DNA topoisomerase inhibitorsp. 207
Cellular responses to stress and the role of p53p. 209
p53 and cycle arrestp. 210
p53 and nucleotide excision repairp. 213
p53 as a damage sensor in replicative senescencep. 214
Replicative senescence and telomeric clocks?p. 214
Telomeres: form and functionp. 215
Telomerasep. 216
p53 and replicative senescencep. 216
Nature of the p53-activating signal at senescence and the role of DNA repair pathways?p. 217
Human cancer-prone disordersp. 220
Perspectivep. 220
Germline disorders involving dominant proto-oncogenes and dominant tumour suppressor genesp. 221
Conclusionsp. 222
Referencesp. 223
Indexp. 233
Table of Contents provided by Syndetics. All Rights Reserved.

ISBN: 9780199637065
ISBN-10: 0199637067
Series: Frontiers in Molecular Biology
Audience: General
Format: Paperback
Language: English
Number Of Pages: 256
Published: 11th November 1999
Country of Publication: GB
Dimensions (cm): 24.61 x 18.9  x 1.4
Weight (kg): 0.47