DNA methylation and mutation

Holliday, Robin; Grigg, G. W.

doi:10.1016/0027-5107(93)90052-h

Cited by 305 publications

(200 citation statements)

References 31 publications

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“…They are significantly (P , 0.001) more frequent than any other types of substitution, including the reverse transitions T / C and T / G. C / T transitions (and G / A transitions on the opposite strand) are the hallmark of spontaneous deamination of 5-methylcytosine (5 m C), which produces a G-T mismatch at the deaminated site. The mismatch can be restored to the G-C pair in one direction, but creates an A-T pair in the other direction (Holliday and Grigg 1993;Finnegan et al 1998), resulting in T / C transitions (and A / G on the opposite strand). This observation is consistent with the known high level of C methylation in plant nuclear DNA (Ayliffe et al 1998) and with assuming no purifying selection on the sequence of ITS2 as may be expected if the ITS-B1-type genes do not contribute to the ribosome population.…”

Section: Resultsmentioning

confidence: 99%

Molecular Evidence for Transcription of Genes on a B Chromosome in Crepis capillaris

et al. 2005

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Dispensable, supernumerary (B) chromosomes are found in diverse eukaryotic species. The origin and genetic consequences of B chromosomes have been the subjects of speculation for more than a century. Until now, there has been no molecular evidence that B chromosome DNA is transcribed and there is no unequivocal evidence as to their origin. B chromosomes are considered to be genetically inert although they appear to cause a variety of phenotypic effects. We report that members of one of two ribosomal RNA gene families that are confined to the B chromosomes of a plant, Crepis capillaris, are transcribed-thus providing the first molecular evidence of gene activity on B chromosomes. Sequence analysis of part of the A and B chromosome rRNA genes, together with comparisons with related species, indicates that the B chromosome rRNA genes originate from the A chromosome.

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Section: Resultsmentioning

confidence: 99%

Molecular Evidence for Transcription of Genes on a B Chromosome in Crepis capillaris

et al. 2005

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“…In higher eukaryotes, DNA is methylated only at cytosines located 5 0 to guanosine in the CpG dinucleotide (Holliday and Grigg, 1993). This modification has important regulatory effects on gene expression, especially when CpG-rich regions, located in the promoter regions of many genes are involved (Bird, 2002).…”

Section: Introductionmentioning

confidence: 99%

CLCA2 tumour suppressor gene in 1p31 is epigenetically regulated in breast cancer

Cowell

Sossey‐Alaoui

2004

Oncogene

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The calcium-activated chloride channel gene family is clustered in the 1p31 region, which is frequently deleted in sporadic breast cancer. Recent studies have indicated the association of the second member of this gene family (CLCA2) with the development of breast cancer and metastasis. We have now shown the absence of expression of CLCA2 in several breast cancer tumours and cell lines, which confirms the results from other reports. When overexpressed in CLCA2-negative cell lines, their tumorigenicity and metastasis capability were significantly reduced, suggesting a tumour suppressor role for CLCA2 in breast cancer. The mechanisms behind the silencing of CLCA2 in breast cancer, however, have not been elucidated to date. Although we were able to identify CLCA2 mutations in breast cancers, somatic mutations are not the major cause of CLCA2 gene silencing. On the other hand, treatment of breast cancer CLCA2-negative cell lines with demethylating agents was able to restore CLCA2 expression, suggesting an epigenetic inactivation of this gene. Bisulphite-sequencing of the promoterassociated CpG island of the CLCA2 gene in breast tumours demonstrated that the absence of expression in these tumours was caused by hypermethylation of the promoter CpG island. In contrast, in breast cancer cell lines, tumours, and control cell lines that express CLCA2, a much lower level, and often absence, of methylation of the promoter were demonstrated. These findings demonstrate that CLCA2 is frequently inactivated in breast cancer by promoter region hypermethylation, which makes it an excellent candidate for the 1p31 breast cancer tumour suppressor gene.

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“…5,6 In higher-order eukaryotic cells, DNA is methylated only at cytosines located 5Ј to guanosine in the CpG dinucleotide. 7 This modification has important regulatory effects on gene expression, especially when involving CpG-rich areas known as CpG islands, located in the promoter regions of many genes. 8,9 Aberrant methylation of CpG islands, which are nor- mally unmethylated, has frequently been documented in immortalized and transformed cells 10 and has been associated with transcriptional inactivation of defined tumor suppresser genes in human cancers.…”

Section: Introductionmentioning

confidence: 99%

Decitabine (5-Aza-2′-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells

2000

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DNA methylation and mutation

Cited by 305 publications

References 31 publications

Molecular Evidence for Transcription of Genes on a B Chromosome in Crepis capillaris

Molecular Evidence for Transcription of Genes on a B Chromosome in Crepis capillaris

CLCA2 tumour suppressor gene in 1p31 is epigenetically regulated in breast cancer

Decitabine (5-Aza-2′-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells

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