Genetics of recombination in the model bacterium Escherichia coli | p. 1 |
Abstract | p. 1 |
Introduction | p. 1 |
Genes and pathways | p. 2 |
The key steps of the homologous recombination reaction | p. 2 |
Alternative pathways of DSB repair | p. 6 |
Homologous recombination in plasmids | p. 7 |
Ligase and polymerase 1 | p. 8 |
Proteins that antagonize homologous recombination | p. 8 |
The repair of DNA lesions | p. 8 |
RecFOR- dependent DNA repair | p. 9 |
RecBC-dependent recombinational repair | p. 10 |
Recombination and replication | p. 11 |
Replication inactivation induces RecA-independent recombination | p. 11 |
Recombination proteins participate in the resetting of replication forks | p. 13 |
Acknowledgments | p. 18 |
References | p. 18 |
Homologous recombination in low dC + dG Gram-positive bacteria | p. 27 |
Abstract | p. 27 |
Proteins required for recombinational repair | p. 27 |
Recombination avenues | p. 34 |
DNA damage recognition | p. 35 |
DNA end-processing | p. 36 |
DSB coordination | p. 37 |
RecA loading, homologous pairing and strand exchange | p. 37 |
Branch migration and resolution | p. 38 |
Horizontal gene transfer | p. 39 |
Transport and uptake of dsDNA or ssDNA | p. 39 |
Fate of the incoming DNA | p. 40 |
Barriers for HGT | p. 46 |
Acknowledgements | p. 46 |
References | p. 46 |
The bacterial RecA protein: structure, function, and regulation | p. 53 |
Abstract | p. 53 |
The role of recombination in DNA metabolism | p. 53 |
The RecA protein of Escherichia coli | p. 54 |
Overview | p. 54 |
Structure | p. 55 |
Binding to DNA | p. 58 |
ATP hydrolysis and RecA filament states | p. 59 |
DNA strand exchange is a multi-step process | p. 61 |
The role of ATP hydrolysis in DNA strand exchange | p. 63 |
Regulation of RecA function | p. 65 |
Autoregulation by the RecA C-terminus | p. 65 |
Proteins that modulate RecA function | p. 67 |
The single-strand DNA binding protein (SSB) | p. 67 |
The RecFOR proteins | p. 67 |
The DinI and RecX proteins | p. 71 |
The PsiB and RdgC proteins | p. 73 |
The UvrD helicase | p. 75 |
Regulation summary | p. 76 |
References | p. 77 |
Biochemistry of eukaryotic homologous recombination | p. 95 |
Abstract | p. 95 |
Introduction | p. 95 |
Homologous recombination in different contexts | p. 97 |
Biochemistry of recombination proteins | p. 98 |
Structure of the presynaptic Rad51 filament | p. 99 |
Presynapsis: different pathways leading to Rad51 filament formation and the function of distinct mediator proteins | p. 103 |
Synapsis: homology search and DNA strand invasion | p. 113 |
Postsynapsis: many subpathways call for context-specific factors | p. 114 |
Regulation of recombination | p. 119 |
Negative regulation of HR and the roles of the Srs2 DNA helicase and MMR | p. 119 |
Post-translational modification of HR proteins | p. 120 |
Conclusion | p. 122 |
Acknowledgements | p. 123 |
References | p. 123 |
DNA helicases in recombination | p. 135 |
Abstract | p. 135 |
Recombination pathways and models | p. 135 |
DNA helicases in mitotic recombination | p. 140 |
Srs2 | p. 141 |
Fbh1 | p. 145 |
Sgs1 | p. 145 |
WRN | p. 147 |
BLM | p. 147 |
Rad3/Rem1 | p. 148 |
Rrm3 and Pif1 | p. 149 |
DNA helicases in meiotic recombination | p. 149 |
Mer3 | p. 150 |
Srs2 | p. 150 |
Sgs1 | p. 151 |
BLM | p. 151 |
Replication and repair helicases | p. 152 |
Mph1 | p. 152 |
HEF/FANCM | p. 152 |
BRIP1/BACH1/FANCJ | p. 153 |
HEL308/MUS308 | p. 153 |
RecQ5ß | p. 154 |
RecQL1 | p. 154 |
Hmi1 | p. 154 |
Conclusions | p. 155 |
Acknowledgements | p. 156 |
References | p. 156 |
Holliday junction resolution | p. 169 |
Abstract | p. 169 |
A brief overview of HJ formation and processing | p. 169 |
The HJ resolvases | p. 172 |
Structural relationships | p. 172 |
Junction recognition and distortion | p. 174 |
Sequence-specific cleavage and the need for branch migration | p. 176 |
The catalysis of cleavage | p. 177 |
Coordination of cleavage events | p. 178 |
Directing the orientation of junction cleavage | p. 179 |
Searching for the elusive nuclear HJ resolvase | p. 180 |
Mus81 | p. 182 |
Mus81 is related to the XPF family of endonucleases | p. 182 |
The substrate specificity of Mus81* | p. 183 |
The role of Mus81* in meiosis | p. 185 |
Mus81 and links to cancer | p. 186 |
Mus81 and DSB repair in vegetative cells | p. 187 |
Mus81 and stalled replication forks | p. 188 |
Mus81 and inter-strand cross-link repair | p. 189 |
Future perspectives | p. 190 |
Acknowledgements | p. 191 |
References | p. 191 |
Replication forks and replication checkpoints in repair | p. 201 |
Abstract | p. 201 |
DNA replication, checkpoint proteins, and chromosome integrity | p. 201 |
Stalled versus collapsed replication forks and fork stabilization versus fork restart | p. 202 |
Sensing stalled forks and checkpoint mediated stabilization of stalled forks | p. 203 |
Replication fork restart and repair mechanisms | p. 205 |
Recombination-mediated fork restart and repair | p. 207 |
Checkpoint-mediated regulation of recombination | p. 207 |
Other fork restart mechanisms: damage tolerance or postreplication repair pathways | p. 208 |
Damage bypass at the fork versus postreplication repair | p. 210 |
Coordination between DNA replication, topology, and chromatin structure | p. 211 |
Acknowledgements | p. 213 |
References | p. 213 |
Sister chromatid recombination | p. 221 |
Abstract | p. 221 |
Introduction | p. 221 |
Homologous recombination: a mechanism with major activity during replication | p. 222 |
What makes a replication fork stall or collapse? | p. 222 |
The role of recombination during DNA replication | p. 224 |
Methods for the measurement of sister-chromatid recombination | p. 226 |
5-Bromodeoxyuridine labelling | p. 227 |
Detection of SCE in circular molecules | p. 227 |
Genetic assays based on direct repeats | p. 228 |
Molecular analysis of SCR | p. 229 |
DNA repair genes required for SCR | p. 230 |
Specific functions required for SCR | p. 235 |
Cohesins | p. 235 |
Other SMC complexes | p. 238 |
The MRX(N) complex | p. 239 |
Concluding remarks | p. 240 |
Acknowledgements | p. 241 |
References | p. 241 |
Mating-type switching in S. pombe | p. 251 |
Abstract | p. 251 |
Fission yeast life cycle | p. 251 |
The pattern of switching | p. 252 |
The mating-type region | p. 253 |
A site- and strand-specific imprint at matl | p. 254 |
Cis-acting elements controlling the imprint | p. 257 |
Trans-acting swi (switch) genes | p. 257 |
Class Ia | p. 258 |
Class lb | p. 260 |
Class II | p. 261 |
The direction of replication model | p. 263 |
Imprinting formation is coupled to DNA replication | p. 264 |
Imprinting protection | p. 267 |
Mating-type switching | p. 267 |
Initiation | p. 268 |
Choice of the donor | p. 269 |
Gene conversion and its resolution | p. 270 |
Mus81 is the essential nuclease resolving sister chromatid recombination | p. 272 |
Outlook and future directions | p. 273 |
Acknowledgements | p. 275 |
References | p. 275 |
Multiple mechanisms of repairing meganuclease-induced double-strand DNAbreaks in budding yeast | p. 285 |
Abstract | p. 285 |
Introduction | p. 285 |
MAT switching in Saccharomyces, a paradigm for DSB repair | p. 286 |
Physical monitoring of MAT switching | p. 287 |
Monitoring of recombination protein binding to the DSB | p. 288 |
Primer extension | p. 289 |
HO and I-SceI-induced ectopic gene conversions and the control ofreciprocal crossing-over | p. 291 |
Most ectopic recombination occurs by SDSA | p. 292 |
Control of crossing-over associated with gene conversion | p. 295 |
Single-strand annealing (SSA) | p. 297 |
Break-induced replication (BIR) | p. 299 |
At least two pathways of BIR can be shown for non-telomere sequences in S. cerevisiae | p. 301 |
RAD51-dependent BIR | p. 302 |
Analysis of BIR using plasmids and transformation assays | p. 303 |
Nonhomologous end-joining (NHEJ) | p. 305 |
Future prospects | p. 308 |
Acknowledgements | p. 308 |
References | p. 308 |
The cell biology of mitotic recombination in Saccharomyces cerevisiae | p. 317 |
Abstract | p. 317 |
Choreography of DNA double-strand break repair | p. 317 |
Cell cycle regulation of recombination foci | p. 321 |
The cellular response to stalled and collapsed DNA replication forks | p. 322 |
Spontaneous foci | p. 324 |
Dynamics of proteins in foci | p. 324 |
Centers of recombinational DNA repair | p. 325 |
Nucleolar exclusion of homologous recombination | p. 326 |
Cohesins | p. 326 |
Molecular switches | p. 326 |
Future perspectives | p. 327 |
References | p. 328 |
The cell biology of homologous recombination | p. 335 |
Abstract | p. 335 |
Introduction | p. 335 |
Cell biological analyses of homologous recombination proteins | p. 336 |
Controlled induction of DNA damage | p. 337 |
Homologous recombination pathways | p. 340 |
Detection and processing of DSBs | p. 340 |
Nucleoprotein filament formation | p. 343 |
Resolution | p. 347 |
Recombination and replication | p. 348 |
The function of DNA damage induced foci | p. 349 |
References | p. 351 |
BRCA2: safeguarding the genome through homologous recombination | p. 363 |
Abstract | p. 363 |
Introduction | p. 363 |
BRCA2: a tumor suppressor with diverse domain structures in different organisms | p. 364 |
BRCA2 in vertebrates | p. 364 |
BRCA2 in non-vertebrate species | p. 365 |
Binding Partners of BRCA2 | p. 366 |
Rad51: the BRC repeats | p. 366 |
Rad51: exon 27-encoded sequences | p. 366 |
DNA | p. 367 |
DSS1 | p. 367 |
PALB2 and other proteins | p. 368 |
BRCA2 and homologous recombination | p. 368 |
Studies in vitro | p. 368 |
Studies in vivo | p. 369 |
BRCA2 is essential for development but dispensable for the survival of cancer cells | p. 370 |
BRCA2 and cancer predisposition in humans | p. 370 |
BRCA2 is essential during embryogenesis | p. 371 |
Tumorigenesis in conditional Brca2 mutants | p. 372 |
How do BRCA2-deficient cells escape genome surveillance checkpoints? | p. 372 |
Conclusions | p. 373 |
Acknowledgments | p. 373 |
References | p. 374 |
Meiotic recombination | p. 381 |
Abstract | p. 381 |
Overview | p. 381 |
Meiosis | p. 381 |
Meiotic chromosome structure and the synaptonemal complex | p. 382 |
Stages of meiotic prophase 1 | p. 384 |
Recombination nodules | p. 384 |
Overview of meiotic recombination | p. 385 |
The pathway of meiotic recombination | p. 385 |
Monitoring meiotic recombination intermediates | p. 385 |
Initiation of meiotic recombination | p. 387 |
The Spo11 complex | p. 387 |
Other factors that Influence DSB formation | p. 394 |
Resection of DSB-ends | p. 398 |
Assembly of the Spo11 complex and triggering of Spo11 cleavage | p. 399 |
Homolog pairing and formation of joint molecules | p. 400 |
Dmc1 | p. 401 |
Assembly of the strand-exchange complex | p. 401 |
The Hop2-Mnd1 complex | p. 403 |
How do strand-exchange proteins promote homolog pairing? | p. 405 |
Strand-exchange and joint molecule formation | p. 406 |
Interhomolog bias | p. 408 |
Suppression of intersister recombination | p. 408 |
Interhomolog only functions | p. 412 |
Crossover control | p. 412 |
Crossover assurance | p. 412 |
Crossover interference | p. 413 |
Crossover and noncrossover pathways | p. 414 |
Pro-crossover factors | p. 414 |
A molecular model of crossover and noncrossover pathways | p. 419 |
Closing remarks | p. 421 |
Acknowledgements | p. 422 |
References | p. 422 |
Site-specific recombination | p. 443 |
Abstract | p. 443 |
Introduction | p. 443 |
The two families of recombinases: tyrosine and serine | p. 445 |
The tyrosine recombinase family | p. 446 |
Topoisomerases and tyrosine recombinase active sites | p. 446 |
Control of the recombination reaction | p. 448 |
Serine family recombinases | p. 451 |
Domain organisation and active site of serine family recombinases | p. 451 |
Mechanism of recombination by serine family recombinases | p. 452 |
Directing recombination outcome | p. 453 |
Accessory proteins, sequences, and topological selectivity | p. 453 |
Recombination between asymmetric accessory sites can give reaction directionality | p. 454 |
Applications of site-specific recombination | p. 456 |
Related proteins | p. 457 |
Large serine recombinases | p. 457 |
Integrons | p. 457 |
Conjugative transposons | p. 459 |
telomeres of linear prokaryotic chromosomes | p. 460 |
Xer recombination: a multifunctional recombination system | p. 461 |
Concluding remarks | p. 462 |
References | p. 463 |
V(D)J recombination: mechanism and consequences | p. 469 |
Abstract | p. 469 |
Introduction | p. 469 |
General properties of V(D)J recombination | p. 470 |
Recombination sites | p. 470 |
The RAG genes and proteins | p. 472 |
DNA cleavage by the RAG proteins | p. 472 |
Coupled cleavage | p. 473 |
RSS recognition | p. 474 |
RAG protein binding to DNA | p. 475 |
DNA transposition by RAG1/2 | p. 476 |
implications of RAG1/2 transposition for the evolution of the immune system and for chromosomal translocations | p. 477 |
Sequence motifs and mutational studies of the RAG proteins | p. 478 |
Other functions of the RAG proteins | p. 479 |
End processing and joining in V(D)J recombination | p. 480 |
References | p. 482 |
Nonhomologous end-joining: mechanisms, conservation and relationship to illegitimate recombination | p. 487 |
Abstract | p. 487 |
Introduction | p. 487 |
DNA mechanisms of nonhomologous end-joining | p. 488 |
Double strand breaks | p. 488 |
Overhang-to-overhang joining | p. 488 |
Blunt end joining and polymerization across the break | p. 490 |
Use of internal microhomologies | p. 490 |
The balance between joining modes | p. 490 |
Protein pathways for nonhomologous end-joining | p. 491 |
Ku- and Lig4-dependent NHEJ | p. 491 |
MMEJ | p. 493 |
SSA and related mechanisms | p. 494 |
SSBR applied to DSBs | p. 495 |
Species conservation of Ku-dependent NHEJ | p. 497 |
Vertebrates and related | p. 497 |
Insects and worms | p. 497 |
S. cerevisiae | p. 498 |
Other fungi | p. 499 |
Protozoa | p. 500 |
Plants | p. 500 |
Bacteria | p. 500 |
Viruses | p. 501 |
NHEJ interplay with host cell processes | p. 502 |
Chromatin | p. 502 |
Checkpoints | p. 503 |
Cell cycle | p. 503 |
Outcomes of NHEJ and its deficiency | p. 504 |
Accurate repair and maintenance of genome integrity | p. 504 |
Adaptive and targeted mutagenesis | p. 504 |
Concluding remarks | p. 505 |
References | p. 505 |
Abbreviations | p. 512 |
Index | p. 515 |
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