Genetic abnormalities downstream of notch signal activation

It would be needless reiteration to say that a signalling process can be deregulated by abnormalities of any one of the components of the machinery. The human SEL1L gene shows sequence homology to sel-1 gene of Caenorhabditis elegans. Sel-1 has been reported to negatively regulate the activity of lin-12 gene, which is implicated in the processes of cell differentiation. It has been suggested on an empirical basis that notch signalling is also negatively regulated by SEL1L gene, which is the...

Alu elements in genetic transcription

Alu elements were once regarded as functionally inert repeats. It was recognised some time ago that they might be functionally active. The presence of Alu sequences in the promoter regions of many genes has suggested a role in genetic transcription. For example, transcription factor binding elements have been identified within Alu sequences. The sequences have been seen as a means of regulating the expression of RNA polymerase II. The frequency and the numbers of such sites encountered have led...

Intrachromosomal recombination in tumour suppressor genes in cancer

Genomic deletions occur in tumour suppressor genes and genes regulating cell proliferation and such mutations are encountered frequently in the pathogenesis and progression of cancer. As discussed elsewhere in this book (see Chapter 3), homologous and non-homologous intrachromosomal recombination or unequal exchanges and recombination between chromatids can bring about the duplication of genetic material, which is often visualised as HSRs or DMs. Drug resistant cell lines contain DMs and HSRs,...

Bcl2 in p53induced apoptosis

The bcl2 and related genes are subject to regulation by the cell proliferation-related p53, which is one of the interacting pathways in the control of apoptosis. The wild-type p53 protein has a wide-ranging function, including regulation of cell cycle arrest, in a transient or sustained way, and regulation of apoptosis and cell senescence. DNA damage induces p53. Two kinases phosphorylate the suppressor protein. One of these is ATM, a 370 kDa protein, which is a member of the PI-3 kinase...

Alumediated interchromosomal recombination in Ewing sarcoma

Gene fusion is a phenomenon arising from interchromosomal reorganisation. The fusion of RET and ELE1 genes occurs in radiation-induced thyroid carcinomas. We know from the investigation by Nikiforov et al. (1999) that the breakpoints culminating in the formation of the fusion gene seem to be distributed in the introns of the genes in a rather random manner. However, they do point out that there is a cluster of breakpoints in the Alu repeats of ELE1 gene. A characteristic reciprocal...

DNA ploidy cell proliferation and growth factor expression

There are fundamental arguments for suggesting that DNA ploidy is a reflection of some basic processes gone astray during cell proliferation. It has been suggested that DNA aneuploidy might be a consequence of cells entering the S-phase prematurely. The close association between aneuploidy and the size of the S-phase fraction (SPF) seems to suggest this. According to Wenger et al. (1993), aneuploid tumours show a virtual doubling of the S-phase fraction. Esteva et al. (2001) have claimed that...

DNA aneuploidy and cancer progression

DNA aneuploidy is often regarded as an indicator of tumour malignancy. Many early reports have indicated a high frequency of DNA aneuploidy in several human neoplasms. This has inevitably led to detailed investigations of the influence of DNA aneuploidy on cancer invasion and metastatic progression and its potential for predicting prognosis. DNA ploidy reportedly correlates with the myometrial invasion by primary endometrial carcinomas. Aneuploid primary tumours also recur more frequently as...

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DNA ploidy, SPF and cell cycle distribution were determined by image cytometry. g0g, g2m represents the ratio of cells occurring in the two cell cycle peaks. Normally only around 10 of cells are found in the G2M peak and > 10 in this peak can be regarded as indicating hyperdiploidy. DNA ploidy, SPF and cell cycle distribution were determined by image cytometry. g0g, g2m represents the ratio of cells occurring in the two cell cycle peaks. Normally only around 10 of cells are found in the G2M...

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Figure 2 DNA-PK Ku proteins in non-homologous end-joining DNA repair. This Figure is a diagrammatic representation of the involvement of DNA-dependent protein kinase DNA-PK in non-homologous end joining DNA repair. Double strand breaks DSB activate DNA-PK. Ku70 80 heterodimer is the DNA targeting regulatory subunit of DNA-PK, and by virtue of its function as a helicase participates in the resolution of aberrant DNA structures. Among cellular proteins that interact with the Ku heterodimer is the...