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Advances in Brief

Repair Defect in p21WAF1/CIP1 -/- Human Cancer Cells

E. Robert McDonald III, Gen Sheng Wu, Todd Waldman and Wafik S. El-Deiry
E. Robert McDonald III
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Gen Sheng Wu
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Todd Waldman
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Wafik S. El-Deiry
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DOI:  Published May 1996
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Abstract

p53 induction and cell cycle arrest occur following DNA damage, possibly to allow repair prior to replication. p21WAF1/CIP1, a cyclin-cyclin-dependent kinase inhibitor and proliferating cell nuclear antigen-interacting protein, is induced by p53 and mediates the cell cycle arrest. To investigate a role for p21 in DNA repair in vivo, we studied the expression of in vitro damaged reporter DNA transfected into p21 +/+ or -/- HCT116 human colon cancer cells. Introduction of UV-damaged or cis-platinum-damaged cytomegalovirus-driven β-galactosidase reporter DNA into tumor cells revealed a significant decrease (2–5-fold) in reporter expression in p21 -/- versus +/+ cells. In the absence of DNA damage, there was a significant increase (2–3-fold) in the number of 6-TG-resistant colonies derived from p21 -/- versus +/+ cells. Reintroduction of wild-type p21, but not a p21 C-terminal truncation mutant which lacks the proliferating cell nuclear antigen interaction domain, stimulated (2–3-fold) the repair capacity of the p21-deficient cells. We conclude that p21 deficiency is associated with a defect in DNA repair, which could lead to an increased sensitivity of tumor cells to DNA damage.

Footnotes

  • ↵1 This work was supported by the Howard Hughes Medical Institute and by NIH Training Grants GM07309 (T. W.) and 5-T32-GM08216 (E. R. M.). W. S. E-D. is an Assistant Investigator of the Howard Hughes Medical Institute.

  • ↵2 The first two authors contributed equally to this work.

  • ↵3 To whom requests for reprints should be addressed, at University of Pennsylvania School of Medicine, Clinical Research Building, Room 437A, 415 Curie Boulevard, Philadelphia, PA 19104-6148. Fax: (215) 573-9139; E-mail: weldeir@hmivax.humgen.upenn.edu.

  • Received December 18, 1995.
  • Accepted March 28, 1996.
  • ©1996 American Association for Cancer Research.
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May 1996
Volume 56, Issue 10
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Repair Defect in p21WAF1/CIP1 -/- Human Cancer Cells
E. Robert McDonald III, Gen Sheng Wu, Todd Waldman and Wafik S. El-Deiry
Cancer Res May 15 1996 (56) (10) 2250-2255;

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Repair Defect in p21WAF1/CIP1 -/- Human Cancer Cells
E. Robert McDonald III, Gen Sheng Wu, Todd Waldman and Wafik S. El-Deiry
Cancer Res May 15 1996 (56) (10) 2250-2255;
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