DNA repair defects

Ulp2 S. cerevisiae increased SUMO conjugates, DNA repair defective desumoylating enzyme [123]... 

Farmer H, McCabe N, Lord CJ et al (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434 917-921... 

Tracco, C., Oliver, F.J., de Murcia, G. and Menissier-de Murcia, J. (1998) DNA repair defect in poly(ADP-ribose) polymerase-deficient cell lines. Nucleic Acids Res., 26, 2644-2649. 

DNA repair knockout Inborn DNA repair defects Incision assay Base modifications... 

Wood RD, Robins P, Lindahl T (1988) Complementation of the Xeroderma Pigmentosum DNA repair defect in cell free extracts. Cell 53 97-106... 

Some Human Hereditary Diseases and Cancers Associated with DNA-Repair Defects... 

There are several genetically determined diseases such as xeroderma pigmentosum (XP), Fanconi s anemia. Bloom s syndrome, ataxiatelangiectasia and porokeratosis Mibelli in which individuals have an increased if not an invariable incidence of cancer (291. These diseases are associated with DNA repair defects, thought to be the cause of the cancer sensitivity (291. In the case of a person with XP, the oversensitivity of the skin to ultraviolet light is inherited and the condition leads to skin cancer. 

Park Y, Gerson SL (2005) DNA repair defects in stem cell function and aging. Annu Rev Med 56 495-508... 

Blunt, T., Finnic, N., Taccioli, G., Smith, G., Demengeot, J., Gotdieb, T., Mizuta, R., Varghese, A., Alt, F., and Jeggo, P. (1995). Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell 80, 813-823. 

Berger NA, Sims JL, Catino DM et al. Poly(ADP-ribose) polymerase mediates the suicide response to massive DNA damage Studies in normal and DNA-repair defective cells. Princess Takamatsu Symp 1983 13 219-226. 

In vitro nifedipine inhibits proliferation of colon cancer cells with a DNA mismatch repair defect that are resistant to 5-fluorouracil. Whether this also... 

Figure 36-22. Mismatch repair of DNA. This mechanism corrects a single mismatch base pair (eg, C to A rather than T to A) or a short region of unpaired DNA. The defective region is recognized by an endonuclease that makes a single-strand cut at an adjacent methylated GATC sequence. The DNA strand is removed through the mutation, replaced, and religated.

DNA repair Because most mutations are very damaging, even the simplest organisms have enzyme systems that repair DNA. These DNA repair systems are important because genetic defects in them can cause some human diseases. 

Defects have been found in these mechanisms that cause various human diseases. For example, patients with the genetic disease xeroderma pigmentosum are especially sensitive to ultraviolet light and develop skin cancer. Skin fibroblasts cultured from these patients have been shown to be defective in DNA repair. 

Spence, J., Sadis, S., Haas, A. L., and Finley, D. A ubiquitin mutant with specific defects in DNA repair and multiubiquitination. Mol Cell Biol, 1995, 35, 1265-73. 

Our approach recently developed utilizes DNA repair- or recombination-deficient mutants of the yeast Saccharomyces cerevisiae [8]. An important feature of many tumor cells is that they have defects in their ability to repair damage to DNA as compared with normal cells, suggesting that agents with selective toxicity towards repair-deficient cells might be potential anticancer agents. 

Inherited mutations that result in defective DNA repair mechanisms are associated with a predisposition to the development of cancer. Some examples of such genetic diseases are ... 

Damage repair DNA repair enzymes may become more efficient in repairing defects caused by cisplatin. 

Defective DNA repair leads to severe clinical manifestations in this congenital autosomal recessive... 

Ataxia telangiectasia is an autosomal recessive disease characterized by neurologic, endocrine, and hepatic abnormalities, as well as a predisposition to malignancy (119). The defect has been traced to a gene on chromosome 11, the ATM gene that codes for a phosphatidylinositol 3-kinase-like protein which is related to the catalytic subunit of DNA-dependent protein kinase. This protein has a role in signal transduction, DNA repair, and control of the cell cycle (120). Affected patients have a defect in cell-mediated immunity. A decrease in semm IgA is seen in a majority of affected patients. IgG2 or total IgG and IgE levels may be decreased, with an increase in IgM. Patients are susceptible to chronic respiratory... 

Ataxia telangiectasia Mutation in gene on chromosome 11, which codes for protein involved in signal transduction, DNA repair, and control of cell cycle. Defect in cell-mediated immunity. Cerebral ataxia and telangiectasias are hallmarks. 

Abbott DW, Thompson ME, Robinson-BenionCetal. BRCAl expression restores radiation resistance in BRCAl-defective cancer cells through enhancement of transcription-coupled DNA repair. J Biol Chem 1999 274 18808-18812. 

The specific interaction of chemicals or radiation with DNA activate cdlular DNA repair processes which appear to play an important role in carcinogenesis. Eukaryotic cells show enhanced repair capacity for repair of viral nucleic add if the host cells are first damaged by chemicals or irradiation. The ihanced susceptibility to cancer of patients with defective repair systems, such as those with xeroderma pigmentosum, suggests that intact repair mechanisms are protective... 

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