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The telomere / by David Kipling. — Oxford ; New York : Oxford University Press, 1995.—(58.1553/K57) |
Contents
Contents
1 Introduction 1
The end-replication problem 2
Potential solutions to the end-replication problem 4
Terminal hairpins 4
Recombination 6
Protein-primed replication 6
Telomerase 9
Unusual aspects of DNA sequence metabolism 10
Circular genomes 11
References 12
2 The cytology of the telomere 14
The telomere defined 14
Organization in the mitotic interphase nucleus 16
Chromosomes occupy discrete domains in the mitotic interphase nucleus 16
Telomeres and the nuclear envelope in mitotic cells 17
Implications of mitotic interphase genome organization for gene expression and replication 20
Telomere behaviour in meiosis 21
Distribution of chiasmata and implications for genetic maps 23
Summary 25
References 26
3 Telomere structure 31
Isolation and characterization of telomeric sequences 31
Direct sequencing of genomic DNA 31
Cross-hybridization as an approach to identifying telomeric Sequences 32
Cloning telomeric DNA 33
Criteria for a sequence being telomeric 34
General features of telomeric sequences 36
Terminal repeat arrays 36
Subterminal sequences 43
Telomeric sequences 44
Lower eukaryotes 44
Insects 55
Vertebrates 56
Plants 56
Biophysical properties of telomeric DNA 59
The guanine tetrad 59
Intramolecular fold-back structures 61
Intermolecular structures 62
Recent advances: from models to crystals 64
Other unusual structures 64
In vivo significance 65
Proteins that recognize structures containing G" G base Pairs 67
Summary 68
References 69
4 Telomerase 78
Identification of telomerase 78
Tetrahymena 78
Oxytricha 79
Euplotes 80
Humans 80
Mice 81
The RNA component of telomerase has a conserved secondary Structure 81
Primer selection by telomerase 82
Telomerase can synthesize telomeric sequences in vivo 84
Telomerase is responsible for programmed healing in vivo 86
Comparison of in vivo and in vitro processivity 87
A translocation step in the telomerase reaction 88
Does telomerase exist in Saccharomyces cerevisiae? 91
Summary 93
References 94
5 Telomere proteins 97
Biochemically identified proteins 98
Oxytricha nova 98
Euplotes crassus 100
Stylonychia 101
Saccharomyces cerevisiae 102
Physarum polycephalum 106
Vertebrates 107
Telomerase 108
Genetic screens for trans-acting factors in S. cerevisiae Estl 109
cdc8， cdcl7， and cdc21 110
Genetic screens in other species 111
What determines telomere length? 111
Summary 113
References 113
6 Genome rearrangements and telomeres 119
Chromosome healing 119
Programmed genome rearrangements 120
The ciliate life cycle 120
Sequence analysis of the sites of breakage and healing Oxytricha nova 122
Tetrahymena thermophila 122
Paramecium 123
Chromatin diminution in Ascaris 123
Non-programmed healing events in other species 124
Humans 124
Plasmodium falciparum 125
Saccharomyces cerevisiae 125
Summary 126
References 127
7 Human telomere loss， ageing， and cancer 130
Telomere loss in cultured human cells 131
Human fibroblast senescence in vitro 132
Human telomeres shorten with age in vivo 134
Telomerase and cell immortality 135
Shortened telomeres are found in some human tumours 136
Can cancer be caused by telomere loss? 136
Telomeres and cellular senescence 137
Cell mortality and the germ:soma division 138
The biology of organismal ageing 139
Summary 140
References 142
8 Chromatin structure and position effects 146
Sex and the single cell 146
The phenotype of silencing at the HM loci 147
The role of RAPI， ORC， and ABF1 in HAt silencing 148
Telomeric position effects 150
Altered chromatin structure at the silent mating-type loci and Telomeres 151
The biochemical nature of silenced chromatin 152
A model for telomeric position effect 154
Position effect variegation in Drosophila 156
The in vivo role of telomeric silencing 157
Telomere position effects on replication 158
Telomeres， silencers， and plasmid segregation: another associated Phenotype 160
Summary 161
References 163
9 Structure and maintenance of Drosophila telomeres 168
Terminal deletions can be obtained in Drosophila 169
The rate of sequence loss is consistent with incomplete Replication 170
HeT-A sequences can transfer to receding ends 171
Consequences of the retroposon model of telomere maintenance 173
How does Drosophila survive? 174
Similarities to and differences from telomere maintenance in yeast estl mutants 176
How many ways are there to replicate a telomere? 178
References 179
10 Telomeres and mammalian genome analysis 181
Terminal repeat array structure in humans 181
Closing the human genetic map with cloned human telomeres 182
Human subtelomeric sequences 183
The human pseudoautosomal telomere 184
Clustering of human VNTR loci in proterminal regions 185
Expansion of the genetic map in telomeric regions of human Chromosomes 185
Telomere-associated chromosome fragmentation in mammalian Cells 186
Some internal (TTAGGG)n arrays may be the remnants of telomere fusion 187
Using telomeric sequences to investigate chromosome structure 188
Cryptic translocations and human genetic disease 189
Fragile sites and telomeres 190
Other cytological abnormalities possibly involving telomeres 193
Comparative structure of mouse telomeres 193
Genetic analysis of mouse telomeres: closing the genetic map 195
Perspective: (TTAGGG)n tract instability and human genetic disease 196
References 205
Index
