Research Topics
Genomes and Genes | P J HastingsSummaryAffiliation: Baylor College of Medicine Country: USA Publications
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Publications
Competition of Escherichia coli DNA polymerases I, II and III with DNA Pol IV in stressed cellsP J Hastings
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
PLoS ONE 5:e10862. 2010..This mutagenesis assay reveals the DNA polymerases operating in DSB repair during stress and also provides a sensitive indicator for DNA polymerase competition and choice in vivo...
Mechanisms of change in gene copy numberP J Hastings
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Nat Rev Genet 10:551-64. 2009..For example, cellular stress might induce repair of broken replication forks to switch from high-fidelity homologous recombination to non-homologous repair, thus promoting copy number change...
Adaptive amplificationP J Hastings
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
Crit Rev Biochem Mol Biol 42:271-83. 2007..Recent advances in our understanding of amplification in bacteria suggests new interpretations of events leading to human copy number variation, as well as evolution in general...
Adaptive mutation and amplification in Escherichia coli: two pathways of genome adaptation under stressMegan N Hersh
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm S809, Mail Stop 225, Houston, TX 77030-3411, USA
Res Microbiol 155:352-9. 2004..Stress-induced genetic changes may underlie much of microbial evolution, pathogenesis and antibiotic resistance, and also cancer formation, progression and drug resistance...
Separate DNA Pol II- and Pol IV-dependent pathways of stress-induced mutation during double-strand-break repair in Escherichia coli are controlled by RpoSRyan L Frisch
Department of Molecular and Human Genetics, Baylor College of Medicine, Baylor College of Medicine, Houston, Texas 77030 3411, USA
J Bacteriol 192:4694-700. 2010..The results identify a second DNA polymerase contributing to stress-induced mutagenesis and show that RpoS promotes mutagenesis by more than the simple upregulation of dinB...
Adaptive amplification and point mutation are independent mechanisms: evidence for various stress-inducible mutation mechanismsP J Hastings
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
PLoS Biol 2:e399. 2004..We suggest that the availability of alternative pathways for genetic/evolutionary adaptation and clonal expansion under stress may be exploited during processes ranging from the evolution of drug resistance to cancer progression...
Identity and function of a large gene network underlying mutagenic repair of DNA breaksAbu Amar M Al Mamun
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 3411, USA
Science 338:1344-8. 2012....
DinB upregulation is the sole role of the SOS response in stress-induced mutagenesis in Escherichia coliRodrigo S Galhardo
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 3411, USA
Genetics 182:55-68. 2009....
On the mechanism of gene amplification induced under stress in Escherichia coliAndrew Slack
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
PLoS Genet 2:e48. 2006..We outline its possible applicability to amplification in humans and other organisms and circumstances...
SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplificationG J McKenzie
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 3411, USA
Mol Cell 7:571-9. 2001..We show that pol IV, together with the major replicase, pol III, can account for all adaptive point mutations at lac. The results identify a role for pol IV in inducible genetic change...
Microbiology and evolution. Modulating mutation rates in the wildSusan M Rosenberg
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Science 300:1382-3. 2003
Role of RecA and the SOS response in thymineless death in Escherichia coliNatalie C Fonville
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
PLoS Genet 6:e1000865. 2010..The data predict the importance of DNA damage-response and HR networks to TLD and chemotherapy resistance in humans...
Mechanisms for recurrent and complex human genomic rearrangementsPengfei Liu
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Curr Opin Genet Dev 22:211-20. 2012..Both nonhomologous end-joining and aberrant replication have significant roles in chromothripsis. As we study CNV, the processes underlying human genome evolution are revealed...
A role for topoisomerase III in a recombination pathway alternative to RuvABCChristopher R Lopez
Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Mol Microbiol 58:80-101. 2005..These data are consistent with a role for topoisomerase III in disentangling recombination intermediates as an alternative to RuvABC to maintain the stability of the genome...
Pathways of resistance to thymineless death in Escherichia coli and the function of UvrDNatalie C Fonville
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 3411, USA
Genetics 189:23-36. 2011..These results define pathways by which cells resist TLD and suggest strategies for combating TLD resistance during chemotherapies...
In pursuit of a molecular mechanism for adaptive gene amplificationP J Hastings
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room T809 Mail Stop 225, Houston, TX 77030 3411, USA
DNA Repair (Amst) 1:111-23. 2002..We explore possible molecular mechanisms of adaptive amplification in the bacterial system and note parallels to chromosomal instability in other systems...
The sigma(E) stress response is required for stress-induced mutation and amplification in Escherichia coliJanet L Gibson
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 3411, USA
Mol Microbiol 77:415-30. 2010..This provides the first report of mutagenesis promoted by sigma(E), and implies that extracytoplasmic stressors may affect genome integrity and, potentially, the ability to evolve...
Gross chromosomal rearrangement mediated by DNA replication in stressed cells: evidence from Escherichia coliJ M Moore
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA
Ann N Y Acad Sci 1267:103-9. 2012..Strains deleted for the genes for three proteins that inhibit RecA activity, psiB, dinI, and recX, all show unaltered amplification, suggesting that if they do downregulate RecA indirectly, this activity does not promote amplification...
Adaptive point mutation and adaptive amplification pathways in the Escherichia coli Lac system: stress responses producing genetic changeSusan M Rosenberg
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, BCM-S809A Mail Stop BCM225, Houston, TX 77030-3411, USA
J Bacteriol 186:4838-43. 2004
Stress-induced mutation via DNA breaks in Escherichia coli: a molecular mechanism with implications for evolution and medicineSusan M Rosenberg
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Bioessays 34:885-92. 2012..New data also suggest a possible harmony between previous, apparently opposed, models for the molecular mechanism. They additionally strengthen the case for anti-evolvability therapeutics for infectious disease and cancer...
Rebuttal: growth under selection stimulates Lac(+) reversion (Roth and Andersson)Susan M Rosenberg
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, BCM-S809A, Mail Stop BCM225, Houston, TX 77030-3411, USA
J Bacteriol 186:4862-3. 2004
Mutability and importance of a hypermutable cell subpopulation that produces stress-induced mutants in Escherichia coliCaleb Gonzalez
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
PLoS Genet 4:e1000208. 2008..e., it is important. We consider a model in which HMS differentiation is controlled by stress responses. Differentiation of an HMS potentially limits the risks of mutagenesis in cell clones...
Frequency of nonallelic homologous recombination is correlated with length of homology: evidence that ectopic synapsis precedes ectopic crossing-overPengfei Liu
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Am J Hum Genet 89:580-8. 2011..To explain this, we propose that the probability of ectopic chromosome synapsis increases with increased LCR length, and that ectopic synapsis is a necessary precursor to ectopic crossing-over...
Mutation as a stress response and the regulation of evolvabilityRodrigo S Galhardo
Department of Molecular and Human Genetics, Baylor College, Houston, Texas 77030 3411, USA
Crit Rev Biochem Mol Biol 42:399-435. 2007..The emerging commonalities in stress-induced-mutation mechanisms provide hope for new therapeutic interventions for all of these processes...
A microhomology-mediated break-induced replication model for the origin of human copy number variationP J Hastings
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
PLoS Genet 5:e1000327. 2009....
Global chromosomal structural instability in a subpopulation of starving Escherichia coli cellsDongxu Lin
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
PLoS Genet 7:e1002223. 2011..These data imply that chromosomal structural changes occur in bursts or showers of instability that may have the potential to drive rapid evolution...
Rebuttal: adaptive mutation in Escherichia coli (Foster)Susan M Rosenberg
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3411, USA
J Bacteriol 186:4853. 2004
Antibiotic-induced lateral transfer of antibiotic resistanceP J Hastings
Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030 3411, USA
Trends Microbiol 12:401-4. 2004..Several commonly used antibiotics induce the SOS response, potentially hastening genetic change and the evolution to resistance of pathogenic populations. The use of such antibiotics should be reconsidered...
Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangementsPengfei Liu
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Cell 146:889-903. 2011..The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle...
Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genomeClaudia M B Carvalho
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
Nat Genet 43:1074-81. 2011..We propose a mechanism that involves both homology-driven events, via inverted repeats, and microhomologous or nonhomologous events...
