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Modulation of Activity of Human Chromatin-Associated Endonucleases on Damaged DNA by Nucleosome Structure

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DNA Repair Mechanisms and Their Biological Implications in Mammalian Cells

Part of the book series: NATO ASI Series ((NSSA,volume 182))

Abstract

The excision repair pathway in mammalian cells is a complex process involving a number of enzymatic steps. My laboratory has focused on the initial endonuclease mediated step. Our approach has been to develop a method to isolate biologically active endonucleases from mammalian nuclei and examine them for specificity of action on DNA containing specific types of damage (e.g., apurinic/apyrimidinic sites, interstrand cross-links, pyrimidine dimers, monoadducts, intercalated adducts). Using this methodology, we have isolated a series of nine chromatin-associated DNA endonucleases from the nuclei of normal human cells. We have been able to detect individual selective activities of these endonucleases on a number of different types of damaged DNA, and have found that different ones of them recognize different types of DNA damage. We have also examined the endonucleases in cells from patients with a number of genetic diseases known to be deficient in DNA repair (i.e., xeroderma pigmentosum and Fanconi’s anemia). The results have indicated different defects associated with the endonuclease(s), depending upon the genetic disease.

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  1. Department of Pathology, UMDNJ - New Jersey-Medical School, Newark, New Jersey, USA

    Muriel W. Lambert & David D. Parrish

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  1. Muriel W. Lambert
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  1. New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA

    Muriel W. Lambert

  2. Institut Gustave Roussy, Villejuif, France

    Jacques Laval

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Lambert, M.W., Parrish, D.D. (1989). Modulation of Activity of Human Chromatin-Associated Endonucleases on Damaged DNA by Nucleosome Structure. In: Lambert, M.W., Laval, J. (eds) DNA Repair Mechanisms and Their Biological Implications in Mammalian Cells. NATO ASI Series, vol 182. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1327-4_27

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  • DOI: https://doi.org/10.1007/978-1-4684-1327-4_27

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