Addition of UV Endonuclease to Permeable XP Cells to Analyze the Relation of Poly(ADPR) Synthesis to DNA Repair
Poly(adenosine diphosphoribose) is synthesized from NAD+ by poly(ADPR) polymerase, which is a tightly bound chromosomal enzyme whose activity is stimulated when cells are treated with various DNA-damaging agents.1–4 The rapid synthesis and degradation of ADP ribose polymers has the potential for causing drastic but reversible alterations in chromatin conformation. Since poly(ADPR) synthesis increases in response to DNA damage, it was proposed that poly(ADPR) might be involved in the DNA repair process, altering chromatin structure so as to make DNA-damaged regions more readily accessible to the enzymes of DNA repair.2–5 Part of this proposal has been confirmed by the demonstration that inhibitors of poly(ADPR) synthesis interfere with the ability of cells to recover and proliferate following DNA damage.6 In addition, cells made NAD+-deficient by nicotinamide starvation are unable to carry out unscheduled DNA synthesis after treatment with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG); they are also unable to reseal DNA strand breaks after treatment with dimethyl sulfate.6,7
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- 5.J.E. Cleaver, Xeroderma pigmentosutin, in “The Metabolic Basis of Inherited Disease,” J.B. Stanbury, J.B. Wyngaarden, and D.S. Fredrickson, eds., McGraw-Hill, New York (1978).Google Scholar
- 7.E.L. Jacobson, D. Juarez, and J.S. Sims, Absence of DNA repair and poly(ADP-ribose) synthesis in NAD-depleted 3T3 cells, Fed. Proc. 39: 1739 (1980).Google Scholar