REGULATION OF THE BREAST CELL DNA SYNTHESOME
乳腺细胞 DNA 合成体的调节
基本信息
- 批准号:6124559
- 负责人:
- 金额:$ 19.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-12-18 至 2001-11-30
- 项目状态:已结题
- 来源:
- 关键词:ADP ribosylation DNA directed DNA polymerase DNA replication SDS polyacrylamide gel electrophoresis adenine phosphoribosyltransferase breast neoplasms cell line chemical kinetics enzyme activity enzyme mechanism enzyme structure enzyme substrate gel mobility shift assay mammary gland molecular weight nucleic acid biosynthesis
项目摘要
DESCRIPTION: The genetic damage which accompanies the development and
progression of breast cancer has been linked to defects in the DNA synthetic
and DNA repair processes of these cells; and these defects correlate with
changes in the physical structure and enzymatic activity of several proteins
used to carry-out DNA synthesis and repair. The investigator's data
indicate that, as compared to normal breast cells, breast cancer cells
exhibit a 3-4-fold higher DNA synthetic rate, a 6-8-fold decrease in
replication fidelity, and have specific structural alterations in several of
the proteins used to carry-out DNA replication. His goal, therefore, is to
establish a clear link between the differences in the DNA synthetic activity
and replication fidelity of normal and malignant breast cells and the
structural changes specific replication essential proteins undergo during
transformation. To accomplish this, he will initially focus on defining the
kinetic, biophysical, and detailed structural properties of the DNA
polymerases and poly(ADP-ribose) polymerase (PARP) by determining: 1)
differences in the kinetic properties of these enzymes between the normal
and malignant breast cells looking specifically at the Km and Vmax for
substrate utilization, substrate specificity, and the proof-reading activity
of the intrinsic 3-5' exonuclease of DNA polymerases delta and epsilon; as
well as the fidelity with which all of the DNA polymerases carry-out DNA
synthesis; 2) differences in the biophysical characteristics of normal and
malignant breast cell DNA polymerases alpha, delta, epsilon and PARP looking
specifically at the molecular weight, Stokes radii, sedimentation
coefficient, isoelectric point, and 2D-PAGE profiles of these enzymes; and
3) differences in the 2D-PAGE tryptic peptide maps of the normal and
malignant breast cell polymerases looking specifically at the role of
phosphorylation, poly(ADP-ribosylation), and primary amino acid sequence in
mediating these differences.
描述:伴随发育和发育的遗传损伤
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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