Hypervariable minisatellite DNA is a hotspot for homologous recombination in human cells

Wahls, Wayne P.; Wallace, Linda J.; Moore, Peter D.

doi:10.1016/0092-8674(90)90719-u

Cited by 215 publications

(117 citation statements)

References 31 publications

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“…56,57 This gene destabilization might be explained by preexisting recombination hot spots or by de novo hot spots arising from chromosomal exchanges. 58,59 Specific DNA sequences enhance the rate of recombination in the genomes of many different organisms.…”

Section: Resultsmentioning

confidence: 99%

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

Papadopoulos

Benter

Anastassiou

et al. 2002

Intl Journal of Cancer

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Some types of cancer have been associated with abnormal DNA fingerprinting. We used random amplified polymorphic DNA (RAPD) to generate fingerprints that detect genomic alterations in human breast cancer. Primers were designed by choosing sequences involved in the development of DNA mutations. Seventeen primers in 44 different combinations were used to screen a total of 6 breast cancer DNA/normal DNA pairs and 6 uveal melanoma DNA/normal DNA pairs. Forty-five percent of these combinations reliably detected quantitative differences in the breast cancer pairs, while only 18% of these combinations detected differences in the uveal melanoma pairs. Fourteen (32%) and 12 (27%) primers generated a smear or did not produce any band patterns in the first and second cases, respectively. Taking into account the ability of RAPD to screen the whole genome, our results suggest that the genomic damage in breast cancer is significantly higher than in uveal melanoma. Our study confirms other reports that the molecular karyotypes produced with random priming, called amplotypes, are very useful for assessing genomic damage in cancer. Genomic instability is a hallmark of neoplastic transformation and a herald of genomic damage. The existence of an additional type of genomic instability has been described, the microsatellite mutator phenotype pathway. Progress in molecular cancer genetics has facilitated the detection of these mutations. In the last decade, representation differential analysis and comparative genomic hybridization (CGH) were added to methods like flow cytometry, restriction fragment length polymorphisms of polymorphic minisatellite loci and allelotyping, a PCR amplification of informative microsatellite loci.Another promising approach has been introduced, arbitrarily primed PCR 1 combined with random amplified polymorphic DNA (RAPD). 2 Both PCR-based techniques, called amplotyping, use fingerprinting to quantitatively and qualitatively evaluate band alterations. 3 This random priming method allows comparison of normal and tumor tissues at a minimum of 20 -40 genome sites in a single PCR, though evidence suggests that the number of compared loci runs into the hundreds if we take into account that a gel band consists of many comigrating fragments. 4,5 It also includes internal controls and detects moderate gains of chromosomal sequences (trisomy/tetrasomy) that would otherwise escape detection.Previously, we addressed the problems of reproducibility and contamination in random priming. In the present work, we used RAPD fingerprinting to assess the genomic damage present in breast cancer and in uveal melanoma cells. For this task, we designed primers based on sequences that are supposed to play an important role in the mechanisms leading to DNA alterations. Human gene mutations appear to be caused by multiple mechanisms whose relative importance is probably governed by local primary and secondary DNA structure. 7 We have searched for consensus sequences located in the immediate vicinity of gene mutations and for "hot s...

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Section: Resultsmentioning

confidence: 99%

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

Papadopoulos

Benter

Anastassiou

et al. 2002

Intl Journal of Cancer

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“…Specific DNA sequences are known to influence recombination in many organisms (Purandare and Patel 1997). In particular, variable number tandem repeats (VNTRs), which have 9-24 bp repeat elements and a total size of 0.1-2 kb and GT/CA dinucleotide repeats have been shown to be hot spots for homologous recombination (Wahls et al 1990;Majewski and Ott 2000). The REP variable (Table 2) most closely resembles VNTRs and is associated with male recombination (Table 3).…”

Section: Discussionmentioning

confidence: 99%

A Sequence-Based Integrated Map of Chromosome 22

Tapper

Morton²,

Dunham³

et al. 2001

Genome Res.

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The near-completion of the sequence for chromosome 22q revolutionizes map integration. We describe a sequence-based integrated map containing 968 loci including 516 known or predicted gene sequences, 317 STSs not included in these sequences, and 135 nonexpressed multinucleotide polymorphisms. The published sequence spans 34.6 Mb, inclusive of gaps estimated to total 1.1 Mb, compared with a top-down estimate of 43 Mb. This discrepancy is discussed, but will not be resolved until more of the genome is analyzed. The radiation hybrid map has 5% error in order and 34% error in location exceeding 1 Mb. The utility of a composite location based on evidence other than sequence is limited to regions not yet sequenced. A genetic map conditional on sequence order was constructed from pairwise lods. Its length of 74.8 cM in males and 80.2 cM in females is slightly less than the previous estimate not constrained by sequence order. Five recombination hot spots are detected, with differences in location between the sexes. Male recombination correlates with repetitive

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“…However, the studies on the biological functions of minisatellites have brought new findings. For example, recent studies on trinucleotide repeats have underscored the importance of repetitive DNA in a variety of biological processes, ranging from recombination to generation of nucleosome positioning signals (36,37). Other observations on tandem repeats have demonstrated that some human minisatellites might serve as regulatory elements for cellular transcription.…”

Section: Discussionmentioning

confidence: 99%

Transcription of Human ABO Histo-blood Group Genes Is Dependent upon Binding of Transcription Factor CBF/NF-Y to Minisatellite Sequence

Kominato¹,

Tsuchiya²,

Hata³

et al. 1997

Journal of Biological Chemistry

111

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We have studied the transcriptional regulatory mechanism of the human histo-blood group ABO genes, and identified DNA cis-elements and trans-activating protein that control the expression of these genes which are important in blood transfusion and organ transplantation. We introduced the 5 -upstream sequence of ABO genes into the promoterless reporter vector and characterized the promoter activity of deletion constructs using transient transfection assays with gastric cancer cell line KATO III cells. The sequence just upstream of the transcription start site (cap site), and an enhancer element, which is located further upstream (between ؊3899 and ؊3618 base pairs ( Histo-blood group ABH(O) antigens, the major alloantigens in humans (1), have been characterized as defined trisaccharide determinants GalNAc␣133(Fuc␣132)Gal␤13 R, Gal␣133(Fuc␣132)Gal␤13 R, and disaccharide determinant Fuc␣132Gal␤13 R for A, B, and H, respectively (2, 3). These structures represent the secondary gene products which are synthesized from the precursor H substrate by ␣133GalNAc (A transferase) and ␣133Gal transferase (B transferase), the primary gene products coded by the functional alleles at the ABO locus (4, 5). Molecular genetic studies of the ABO genotypes have identified two critical single-base substitutions between A and B genes, the resultant 2-amino acid substitutions being responsible for the different donor nucleotide-sugar substrate specificity between A and B transferases. A single base deletion, which shifts the codon reading frame and abolishes the function of A transferase, has been identified in O allelic cDNAs (6, 7).ABH antigens are known to undergo drastic changes during development, differentiation, and maturation. Studies of these antigens in stratified squamous epithelia provided one of the clearest examples of differential expression during cell maturation (8). In non-keratinized stratified squamous epithelia, the immature cells in the basal layers are characterized by the expression of sialylated or unsubstituted precursor peripheral cores, while differentiated and mature cells in the upper layers sequentially express ␣132-fucosylated H structures, and A and B antigens depending on the ABO genotype of the individual. This sequential expression of carbohydrate antigens is associated with the differentiation pattern of the epithelium. An interesting question is how these changes are controlled during cell differentiation. Since keratinocytes are known to greatly change their gene expression during terminal cell differentiation (9), the switch-on of the ABO genes during the maturation may be governed by the same factor(s). To fill in the gap between the expression of the ABO genes and the appearance of the ABO phenotypes in the terminal differentiation of epithelial cells, it is essential to understand the transcriptional regulatory mechanism of the ABO genes. In addition to the normal cell differentiation process, the changes of ABH antigen expression have also been documented in abnormal processes such as tumorig...

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Hypervariable minisatellite DNA is a hotspot for homologous recombination in human cells

Cited by 215 publications

References 31 publications

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

A Sequence-Based Integrated Map of Chromosome 22

Transcription of Human ABO Histo-blood Group Genes Is Dependent upon Binding of Transcription Factor CBF/NF-Y to Minisatellite Sequence

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