Oncogene from Human EJ Bladder Carcinoma Is Located on the Short Arm of Chromosome 11

A subset of xeroderma pigmentosum (XP) group E cells lack a factor that binds to DNA damaged by UV radiation. This factor can be purified to homogeneity as p125, a 125-kDa polypeptide. However, when cDNA encoding p125 is translated in vitro, only a small fraction binds to UV-damaged DNA, suggesting that a second factor is required for the activation of p125. We discovered that most hamster cell lines expressed inactive p125, which was activated in somatic cell hybrids containing human chromosome region 11p11.2-11cen. This region excluded p125 but included p48, which encodes a 48-kDa polypeptide known to copurify with p125 under some conditions. Expression of human p48 activated p125 binding in hamster cells and increased p125 binding in human cells. No such effects were observed from expression of p48 containing single amino acid substitutions from XP group E cells that lacked binding activity, demonstrating that the p48 gene is defective in those cells. Activation of p125 occurred by a "hit-and-run" mechanism, since the presence of p48 was not required for subsequent binding. Nevertheless, p48 was capable of forming a complex with p125 either bound to UVdamaged DNA or in free solution. It is notable that hamster cells fail to efficiently repair cyclobutane pyrimidine dimers in nontranscribed DNA and fail to express p48, which contains a WD motif with homology to proteins that reorganize chromatin. We propose that p48 plays a role in repairing lesions that would otherwise remain inaccessible in nontranscribed chromatin.

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“…To identify this activating gene, binding activity was measured in several hamster-human hybrid cell lines (13,14,28,31) (Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

Hwang

Toering²,

Francke

et al. 1998

Molecular and Cellular Biology

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147

156

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“…The two genes therefore occur on different chromosomes in both mice and humans. In contrast, the Ha-ras-1 oncogene cosegregates with int-2 on mouse chromosome 7 (20,32) and human chromosome 11 (5), albeit relatively distant from one another (llplS and 11q13, respectively) (5,18,35). Neither gene is particularly close to the deletion involved in Wilms' tumor (18), but the identification of a series of fairly common RFLPs, detailed in Fig.…”

Section: Discussionmentioning

confidence: 99%

Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene.

Casey¹,

Smith²,

McGillivray³

et al. 1986

Mol. Cell. Biol.

165

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int-2 is one of two cellular genes (int-i and int-2) currently implicated in the genesis of mammary carcinomas by mouse mammary tumor virus and may constitute a novel cellular proto-oncogene. Using low-stringency hybridization with mouse int-2 probes, we established that homologous genes exist in a variety of mammalian species, including humans, but failed to detect related sequences in other classes and phyla. Recombinant bacteriophage clones and a single cosmid encompassing the human int-2 gene were isolated and characterized by restriction enzyme mapping. A survey of nine primary human breast tumors, three breast tumor cell lines, and three normal individuals revealed no evidence for gross amplification or rearrangement of the int-2 locus. Three distinct restriction fragment length polymorphisms were observed which could prove useful in future linkage studies. By a combination of in situ hybridization of metaphase chromosomes and somatic cell genetics, the human int-2 gene was mapped to chromosome 11, band q13.

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“…Several genes such as the human 83-globin gene cluster (HBBC), the parathyroid hormone (PTH) gene, the oncogene HRASI (formerly termed c-Ha-ras-1), and the insulin gene have been assigned to the short arm of chromosome 11 (1)(2)(3)(4)(5). By using DNA polymorphisms for linkage analysis, it has been shown that PTH, HBBC, HRASI, and the insulin gene are closely linked to each other (6,7).…”

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confidence: 99%

Linkage map of the short arm of human chromosome 11: location of the genes for catalase, calcitonin, and insulin-like growth factor II.

Kittur

Höppener

Antonarakis

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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The following order of genes on the short arm of human chromosome 11 (lip) was determined previously: parathyrold hormone (PTH)-the ,3-globin gene cluster (HBBC-HRASl/insulin. Although it is generally agreed that HRASI (formerly termed c-Ha-ras-1) and the insulin gene are close to each other [14 centimorgans (cM)], their order on chromosome 11p is still in question. We have now added three other genes, those for catalase, calcitonin, and insulin-like growth factor II (IGF-H), to this map of chromosome lip by use of restriction site polymorphisms adjacent to these genes in classical linkage analysis. Most importantly, we find no evidence of linkage between the catalase and HBBC loci. In addition, our data indicate that the calcitonin gene is located between the catalase gene and the PTH gene. Our best estimate of the distance between the catalase and calcitonin genes is -16 cM, while that between the calcitonin and PTH genes is =8 cM. In agreement, very loose linkage was found between the catalase and PTH loci (%26 cM). Since the catalase locus has been mapped to lipl3, these data support the view that the PTH, HBBC, HRASI, and insulin loci are located on the distal short arm of chromosome 11. The IGF-II gene is tightly linked to both the HRASI oncogene and the insulin gene since no recombinants were observed between the IGF-II and the HRASI/insulin loci. Thus, based on our linkage analysis we propose that the most likely gene order for the short arm of chromosome 11 is centromere-catalase-calcitonin-PTH-HBBC-HRASI/insulin-telomere and that the IGF-II gene is very close to both the HRASI and the insulin genes.

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Oncogene from Human EJ Bladder Carcinoma Is Located on the Short Arm of Chromosome 11

Cited by 98 publications

References 29 publications

p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene.

Linkage map of the short arm of human chromosome 11: location of the genes for catalase, calcitonin, and insulin-like growth factor II.

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