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2.
Environ Mol Mutagen ; 49(4): 308-11, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18366099

RESUMO

Recent data shows that the effects of ionizing radiation are not restricted to the directly exposed parental germ cells, but can also manifest in their nonexposed offspring, resulting in elevated mutation rates and cancer predisposition. The mechanisms underlying these transgenerational changes remain poorly understood. One of the most important steps in elucidating these mechanisms is to investigate the initial cellular events that trigger genomic instability. Here we have analyzed the effects of paternal treatment by ethylnitrosourea, an alkylating agent which is known to form specific types of DNA adducts, on the transgenerational effects in the first-generation (F1) offspring of exposed CBA/Ca and BALB/c male mice. Mutation rates at two expanded simple tandem repeat loci were significantly elevated in the F1 germline of both strains. Pre and postmeiotic exposures resulted in similar increases in mutation rate in the F1 germline. Within each strain mutation rates were equally elevated in the germline of male and female F1 offspring of the directly exposed males. The results of our study suggest that transgenerational instability is not attributed to a specific sub-set of DNA lesions, such as double strand breaks, and is most probably triggered by a stress-like response to a generalized DNA damage.


Assuntos
Alquilantes/toxicidade , DNA/efeitos dos fármacos , Etilnitrosoureia/toxicidade , Instabilidade Genômica , Exposição Paterna/efeitos adversos , Animais , DNA/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA
3.
Science ; 316(5833): 1895-8, 2007 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-17600215

RESUMO

Circadian and other natural clock-like endogenous rhythms may have evolved to anticipate regular temporal changes in the environment. We report that a mutation in the circadian clock gene timeless in Drosophila melanogaster has arisen and spread by natural selection relatively recently in Europe. We found that, when introduced into different genetic backgrounds, natural and artificial alleles of the timeless gene affect the incidence of diapause in response to changes in light and temperature. The natural mutant allele alters an important life history trait that may enhance the fly's adaptation to seasonal conditions.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Fotoperíodo , Estações do Ano , Seleção Genética , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Ritmo Circadiano/genética , Proteínas de Drosophila/fisiologia , Europa (Continente) , Evolução Molecular , Feminino , Geografia , Haplótipos , Dados de Sequência Molecular , Mutação , Filogenia , Polimorfismo Genético , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Reprodução , Temperatura , Transformação Genética
4.
Mutat Res ; 617(1-2): 147-51, 2007 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-17331550

RESUMO

Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of mismatch repair deficient Msh2 knock-out mice. Spontaneous mutation rates in homozygous Msh2(-/-) males were significantly higher than those in isogenic wild-type (Msh2(+/+)) and heterozygous (Msh2(+/-)) mice. In contrast, the irradiated Msh2(-/-) mice did not show any detectable increases in their mutation rate, whereas significant ESTR mutation induction was observed in the irradiated Msh2(+/+) and Msh2(+/-) animals. Considering these data and the results of other publications, we propose that the Msh2-deficient mice possess a mutator phenotype in their germline and somatic tissues while the loss of a single Msh2 allele does not affect the stability of heterozygotes.


Assuntos
Mutação em Linhagem Germinativa/efeitos da radiação , Proteína 2 Homóloga a MutS/genética , Radiação Ionizante , Sequências de Repetição em Tandem/genética , Animais , Feminino , Heterozigoto , Homozigoto , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 2 Homóloga a MutS/deficiência , Tolerância a Radiação
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