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
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↵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.
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↵2 The first two authors contributed equally to this work.
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↵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.
Volume 56, Issue 10
