RESUMO
A tof1 mutant was recovered in a screen aimed at identifying genes involved specifically in the S phase branch of the MEC1-dependent DNA damage response pathway. The screen was based on the observation that mutants missing this branch are particularly dependent on the cell cycle-wide branch and, therefore, on RAD9, for surviving DNA damage. tof1 and rad9 conferred synergistic sensitivity to MMS, UV, and HU, and the double mutant was incapable of slowing S phase in response to MMS, inducing RNR3 transcription in response to UV, and phosphorylating Rad53p in response to HU. TOF1's contribution to DNA damage response appeared to be restricted to S phase, since TOF1 did not contribute to UV-induced transcription during G1 or to the cdc13-1-induced block to anaphase in G2/M. I suggest a model in which Tof1p functions to link Mec1p with Rad53p.
Assuntos
Dano ao DNA/genética , Proteínas Fúngicas/fisiologia , Proteínas Serina-Treonina Quinases , Fase S/genética , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Proteínas de Ciclo Celular/genética , Divisão Celular , Quinase do Ponto de Checagem 2 , Ciclina B/genética , Proteínas de Ligação a DNA , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Citometria de Fluxo , Proteínas Fúngicas/genética , Genótipo , Hidroxiureia , Peptídeos e Proteínas de Sinalização Intracelular , Metanossulfonato de Metila , Modelos Genéticos , Mutagênicos , Mutação , Proteínas Quinases/genética , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genética , Transcrição Gênica/efeitos da radiação , Raios UltravioletaRESUMO
According to the model of FOSS, LANDE, STAHL and STEINBERG, chiasma interference is a reflection of the requirement for crossovers to be separated by an organism-specific number of potential conversion events without associated crossovers. This model predicts that tetrads with close double crossovers should be enriched for conversion events that themselves are not associated with crossing over. We tested this prediction in Saccharomyces cerevisiae and found it to be unfulfilled.
Assuntos
Troca Genética/genética , Meiose/genética , Modelos Genéticos , Recombinação Genética/genética , Saccharomyces cerevisiae/genética , Cromátides/genética , Cromossomos Fúngicos/genética , Marcadores Genéticos , MatemáticaRESUMO
For many organisms, meiotic double crossing over is less frequent than expected on the assumption that exchanges occur at random with respect to each other. This "interference," which can be almost total for nearby intervals, diminishes as the intervals in which the double crossovers are scored are moved farther apart. Most models for interference have assumed, at least implicitly, that the intensity of interference depends inversely on the physical distance separating the intervals. However, several observations suggest that interference depends on genetic distance (Morgans) rather than physical distance (base pairs or micrometers). Accordingly, we devise a model in which interference is related directly to genetic distance. Its central feature is that recombinational intermediates (C's) have two fates--they can be resolved with crossing over (Cx) or without (Co). We suppose that C's are distributed at random with respect to each other (no interference); interference results from constraints on the resolution of C's. The basic constraint is that each pair of neighboring Cx's must have between them a certain number of Co's. The required number of intervening Co's for a given organism or chromosome is estimated from the fraction of gene conversions that are unaccompanied by crossover of flanking markers. The predictions of the model are compared with data from Drosophila and Neurospora.
Assuntos
Troca Genética/genética , Recombinação Genética , Animais , Drosophila melanogaster/genética , Ligação Genética , Matemática , Meiose/genética , Modelos Genéticos , Neurospora crassa/genéticaRESUMO
The process designated RIP (repeat-induced point mutation) alters duplicated DNA sequences in the sexual cycle of Neurospora crassa. We tested whether non-Neurospora sequences are susceptible to RIP, explored the basis for the observed immunity to this process of a diverged tandem duplication that probably arose by a natural duplication followed by RIP (the Neurospora zeta-eta region), and investigated whether RIP extends at all into unique sequences bordering a duplicated region. Bacterial sequences of the plasmid pUC8 and of a gene conferring resistance to hygromycin B were sensitive to RIP in N. crassa when repeated in the genome. When the entire 1.6-kb zeta-eta region was duplicated, it was susceptible to RIP, but was affected by it to a lesser extent than other duplications. Only three of 62 progeny from crosses harboring unlinked duplications of the region showed evidence of changes. We attribute the low level of alterations to depletion of mutable sites. The stability of the zeta-eta region in strains having single copies of the region suggests that the 14% divergence of the tandem elements is sufficient to prevent RIP. DNA sequence analysis of unduplicated pUC8 sequences adjacent to a duplication revealed that RIP continued at least 180 bp beyond the boundary of the duplication. Three mutations occurred in the 200-bp segment of bordering sequences examined.
Assuntos
Família Multigênica , Mutagênese Sítio-Dirigida , Neurospora crassa/genética , Sequências Repetitivas de Ácido Nucleico , Sequência de Bases , Southern Blotting , Cruzamentos Genéticos , Metilases de Modificação do DNA/genética , Variação Genética/genética , Dados de Sequência Molecular , Plasmídeos/genética , Sensibilidade e Especificidade , Homologia de Sequência do Ácido Nucleico , Transformação GenéticaRESUMO
Many musculoskeletal abnormalities in the pelvis are first seen by body imagers while reviewing pelvic cross-sectional studies, and some of these abnormalities may mimic malignancy or another aggressive process. This article describes nine musculoskeletal pseudotumours and interpretative pitfalls that may be seen on CT, MRI and ultrasound imaging of the pelvis. Awareness of these pitfalls and pseudotumours may help avoid misdiagnosis and prevent inappropriate intervention or management.
Assuntos
Diagnóstico por Imagem , Doenças Musculoesqueléticas/diagnóstico , Pelve , Estudos Transversais , Erros de Diagnóstico/prevenção & controle , Humanos , Imageamento por Ressonância Magnética/métodos , Músculo Esquelético/transplante , Neoplasias/diagnóstico , Ossificação Heterotópica , Cistos de Tarlov/diagnóstico , Tendinopatia/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
The direct detection of gonococcal DNA in rectal and pharyngeal specimens was evaluated by using a DNA probe-based assay (Gen-Probe, Inc., San Diego, Calif.). Rectal (234) and pharyngeal (608) swab specimens were obtained from 249 men and 372 women attending sexually transmitted disease clinics in Las Vegas and Reno, Nevada. The prevalence of gonococcal infection by culture at the pharyngeal and rectal sites was 2.9% (16 of 548 specimens) in women and 2.7% (8 of 294 specimens) in men. No false-positive reactions were observed among the 234 rectal specimens tested. Two probe-positive, culture-negative specimens were detected among the 361 pharyngeal specimens obtained from women. Both of these samples were confirmed as Neisseria gonorrhoeae by a probe competition assay. The overall correlation of the DNA probe test with pharyngeal and rectal cultures was 99.4% (837 of 842 cultures), with a sensitivity of 87.5% (21 of 24 cultures) and specificity of 99.7% (816 of 818 cultures). The positive and negative predictive values of the DNA assay were 91.3 and 99.8%, respectively. The direct DNA probe assay provides an alternative to culture screening for rectal and/or pharyngeal gonococcal infections.