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Biomedical subjects

M A Lagarkova

Publications and source records attributed to M A Lagarkova.

8 recordsLinked to original sources
PubMed2001

Cloning and characterization of TNKL, a member of tankyrase gene family.

By serological screening of a breast tumor cDNA library we have identified a novel human gene, tnkl, encoding an ankyrin-related protein with a high degree of similarity to tankyrase, the poly(ADP-ribose)polymerase associated with human telomeres (Smith et al, Science 282: 1484). The tnkl gene maps to chromosome 10, while the tnks gene encoding tankyrase is located on chromosome 8. The predicted 1166-aa protein product of the tnkl gene is 78% identical to human tankyrase and 62% to a putative D. melanogaster protein. Since the proteins have essentially identical domain structures, the corresponding genes form a distinct gene family. The possible link between TNKL and cancer justifies its further functional analysis.

Amino Acid Sequence↗
PubMed2000

Human cortactin as putative cancer antigen.

Humoral immune response against overexpressed oncogenic or tumor supressor proteins has been demonstrated for many types of cancer. In this study we report on the detection of the autologous antibody response to putative oncogene, human cortactin using serological analysis of breast carcinoma expression library. Cortactin maps to chromosome 11q13, the region amplified in about 15% of primary breast carcinomas and 30% of head and neck squamous cell carcinomas. Cortactin overexpression due to such amplification might affect adhesive properties of human cancer cells and is associated with poor disease prognosis. Accordingly, we detected overexpression of cortactin transcript in autologous tumor and amplification/overexpression of cortactin in tumors of breast cancer patients serologically positive for this marker. We demonstrate that 15% of breast cancer patients elicit humoral immune response against human cortactin.

Amino Acid Sequence↗
PubMed1998

DNA loop anchorage region colocalizes with the replication origin located downstream to the human gene encoding lamin B2.

The recently developed procedure of topoisomerase II-mediated DNA loop excision has been used to analyze the topological organization of a human genome fragment containing the gene encoding lamin B2 and the ppv1 gene. A 3.5 kb long DNA loop anchorage/topoisomerase II cleavage region was found within the area under study. This region includes the end of the lamin B2 coding unit and an intergenic region where an origin of DNA replication was previously found. These observations further corroborate the hypothesis that DNA replication origins are located at or close to DNA loop anchorage regions.

Binding Sites↗
PubMed1995

Excision of chromosomal DNA loops by treatment of permeabilised cells with Bal 31 nuclease.

The specificity of long-range fragmentation of human nucleolar genes by Bal 31 nuclease was studied using fractionation of cleavage products by pulsed field gel electrophoresis, followed by Southern hybridization. It was found that limited treatment of permeabilised cells with this nuclease results in accumulation of DNA scissions in matrix attachment areas. Consequently, chromosomal DNA loops and their oligomers are released from the genome.

Cell Line↗
PubMed1995

Large-scale fragmentation of mammalian DNA in the course of apoptosis proceeds via excision of chromosomal DNA loops and their oligomers.

It has been shown recently that apoptotic degradation of genomic DNA in mammalian cells starts by excision of large DNA fragments ranging in size from 50 kilobases to more than 300 kilobases. Although it was suggested that the above fragments could represent chromosomal DNA loops, the supposition was not supported by direct experimental evidence. In present work, we have studied the specificity of nucleolar and euchromatic gene long-range fragmentation in mouse and human cells triggered to undergo apoptosis either by tumor necrosis factor or by serum deprivation. Separation of the excised large DNA fragments by pulsed field gel electrophoresis followed by Southern analysis has demonstrated that in all cases studied the above fragmentation proceeds in a specific way. Furthermore, the patterns of DNA long-range fragmentation in the cells undergoing apoptosis were indistinguishable from the patterns of DNA cleavage into chromosomal loops by the high salt-insoluble topoisomerase II of the nuclear matrix. These results suggest the conclusion that apoptotic degradation of chromosomal DNA starts by excision of DNA loops and their oligomers.

Animals↗
PubMed1995

The specificity of human lymphocyte nucleolar DNA long-range fragmentation by endogenous topoisomerase II and exogenous Bal 31 nuclease depends on cell proliferation status.

The specificity of nucleolar DNA organization into loops in normal and activated to proliferation human lymphocytes has been studied using two different procedures of DNA loop excision. In the activated lymphocytes the nucleolar genes were found to be organized into loops of the same size as the size of individual rDNA repeat. The loops could be excised from the genome by DNA cleavage at matrix attachment sites with either the endogenous topoisomerase II or an exogenous nuclease Bal 31. In normal lymphocytes none of these enzymes generated any specific pattern of nucleolar gene long-range fragmentation, indicating that proliferation arrest correlates with a certain reorganization at higher orders of DNA packaging.

Cell Division↗