Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 5/genética , Leucemia Monocítica Aguda/genética , Proteínas do Tecido Nervoso/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Translocação Genética , Adulto , Humanos , Hibridização in Situ Fluorescente , Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/terapia , MasculinoRESUMO
Common fragile sites are nonrandom loci that show gaps and breaks when cells are exposed to specific compounds. They are preferentially involved in recombination, chromosomal rearrangements, and foreign DNA integration. These sites have been suggested to play a role in chromosome instability observed in cancer. In this work we used a FISH-based approach to identify a BAC contig that spans the FRA2G fragile site located at the 2q31 region. Our observations indicate that a very fragile region spanning at least 450 kb is present within a large fragile region that extends over 1 Mb. At least seven genes are mapped in the fragile region. One of these seems to be a good candidate as a potential tumor suppressor gene impaired by the recurrent deletions observed at the 2q31 region in some neoplasms. In the fragile region, a considerable number of regions of high flexibility that may be related to the fragility are present.
Assuntos
Fragilidade Cromossômica , Cromossomos Artificiais Bacterianos , Ilhas de CpG/genética , Humanos , Hibridização in Situ FluorescenteRESUMO
In this study we have used FISH to examine the relationship between a group of homeobox genes, namely DLX1/DLX2, EVX2 and four HOXD genes (10, 11, 12, 13), that map to region q31 on chromosome 2, and the FRA2G and FRA2H fragile sites located at 2q31 and 2q32.1 respectively. Our results indicate that these homeobox genes lie between the two fragile regions.
Assuntos
Fragilidade Cromossômica/genética , Cromossomos Humanos Par 2/genética , Genes Homeobox/genética , Proteínas de Homeodomínio , Família Multigênica/genética , Afidicolina/farmacologia , Quebra Cromossômica/genética , Sítios Frágeis do Cromossomo , Sondas de DNA , Humanos , Hibridização in Situ Fluorescente , Indóis , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Mapeamento Físico do CromossomoAssuntos
Fragilidade Cromossômica , Cromossomos Humanos Par 2/genética , Colágeno/genética , Proteínas Musculares/genética , Bandeamento Cromossômico , Sítios Frágeis do Cromossomo , Mapeamento Cromossômico , Cromossomos Humanos Par 2/ultraestrutura , DNA Complementar , Corantes Fluorescentes , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente , Indóis , Substâncias IntercalantesRESUMO
This paper reports the results of an investigation into the relationship between common fragile sites and sister chromatid exchanges (SCE). Human leukocyte cultures were grown in two different media, one complete (RPMI 1640) and one deficient in folic acid and thymidine (199M). Some of the cultures were treated with DAPI, a non-intercalating compound which binds preferentially to the AT bases of DNA and is capable of inducing fragile sites. Bromodeoxyuridine (BrdU) was added to all the cultures for SCE analysis. Chromomycin A3 was used for mapping lesions and SCEs by R-banding. A total of 400 cells was examined. The main results show that: BrdU, probably by re-equilibrating the unbalanced nucleotide pool of the 199 culture medium, interferes with the synergism between this culture medium and DAPI in inducing the expression of fragile sites; the SCE frequency per cell is not increased by DAPI in both culture media, therefore this compound does not seem to cause any damage to the DNA and seems merely to act by inhibiting the normal condensation of a subset of fragile sites that possess DAPI-specific base sequences; even in the absence of chromosomal lesions, the fragile sites are significantly preferred as SCE sites to non-fragile sites, whereas in the presence of a lesion, both fragile and non-fragile sites have the same likelihood of undergoing SCE. All this indicates that the presence of a lesion strongly favours SCE formation and that common fragile sites are probably chromosome regions preferentially damaged during the S phase.
