1,720,992 research outputs found
Altered replication timing of the frataxin gene in the presence of the GAA/TTC repeat expansion
No full textThe replication profile of different human cell types, as evaluated by molecular combing at whole genome level and at single loci
No full textGeneral and specific replication profiles are detected in normal human cells by genome-wide and single-locus molecular combing
No full textMammalian genomes are replicated under a flexible program, with random use of origins and variable fork rates, and many details of the process must be still unraveled. Molecular combing provides a set of direct data regarding the replication profile of eukaryotic cells: fork rates; organization of the replication clusters; proportion of unidirectional forks; and fork dynamics. In this study the replication profiles of different primary and immortalized non-cancer human cells (lymphocytes, lymphoblastoid cells, fibroblasts) were evaluated at the whole-genome level or within reference genomic regions harboring coding genes. It emerged that these different cell types are characterized by specific replication profiles. In primary fibroblasts, a remarkable fraction of the mammalian genome was found to be replicated by unidirectional forks, and interestingly, the proportion of unidirectional forks further increased in the replicating genome along the population divisions. A second difference concerned in the proportion of paused replication forks, again more frequent in primary fibroblasts than in PBL/lymphoblastoid cells. We concluded that these patterns, whose relevance could escape when genomic methods are applied, represent normal replication features. In single-locus analyses, unidirectional and paused replication forks were highly represented in all genomic regions considered with respect to the average estimates referring to the whole-genome. In addition, fork rates were significantly lower than whole-genome estimates. Instead, when considering the specificities of each genomic region investigated (early to late replication, normal or fragile site) no further differentiating features of replication profiles were detected. These data, representing the integration of genome-wide and single-locus analyses, highlight a large heterogeneity of replication profiles among cell types and within the genome, which should be considered for the correct use of replication datasets
REPLICATION PROFILE OF THE FXN LOCUS IN NORMAL HUMAN CELLS AND IN MUTATED CELLS CARRYING THE GAA/TCC-REPEAT EXPANSION
No full textReplication profile of the FXN locus in normal human cells and in cells carrying the allele with GAA/TCC-repeat expansion
No full textChromosome Imbalances in Cancer: Molecular Cytogenetics Meets Genomics
No full textGenomic instability is a hallmark of cancer, and it is well-known that in several cancers the karyotype is unstable and rapidly evolving. Molecular cytogenetics has contributed to the description and interpretation of cancer karyotypes, in particular through multicolor FISH approaches which can define even complex chromosome rearrangements. The introduction of genome-wide methods has made available a powerful set of tools with higher resolution than cytogenetics, thus appropriate to comprehend the huge variability of cancer cells. This review focuses on novel findings deriving from the combination of cytogenetic and genomic approaches in cancer research.</jats:p
DNA replication at common fragile site FRA6E under normal and aphidicolin-induced stress conditions
No full textCommon fragile sites (CFSs) are expressed as breaks or gaps on metaphase chromosomes after partial inhibition of the DNA replication process, as induced by aphidicolin. Up to date, several studies suggest that the fragility at these loci may be related to the incomplete replication of the region. FRA6E is one among the most frequently expressed fragile sites of the human genome, and PARK2 is the most relevant gene mapped inside. By molecular combing, we have evaluated the replication pattern of FRA6E under normal and aphidicolin-induced stress conditions in primary human lymphocytes
Rad54/Rad54B deficiency is associated to increased chromosome breakage in mouse spermatocytes
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