Abstract
Postulated roles for p21Waf1/Cip1/Sdi1 (p21) in DNA repair and apoptosis remain controversial. Studies suggest both stimulatory and inhibitory effects of p21 in DNA repair. p21 has also been implicated in induction or protection from apoptosis. Using the tetracycline inducible expression system, we studied the role of p21 in DNA repair and apoptosis in wild-type p53 deficient DLD1 colorectal carcinoma cells. These cells displayed marked heterogeneity in their ability to tolerate higher levels of exogenous p21. The majority of the p21 overexpressing cells grew slower and did not exhibit apoptotic phenotype, some cells underwent apoptotic death within 5 – 8 days following p21 induction while other became giant cells prior to undergoing cell death. Induction of p21 transgene neither sensitized to nor protected from adriamycin-induced acute cell death. p21 also did not alter the clonogenic survival following adriamycin treatment. Clonogenic survival after u.v.-irradiation was, however, increased when p21 expression was transiently induced a few hours before and after u.v.-irradiation. Consistent with its effect on clonogenic survival, p21 also enhanced the cellular capacity to repair three different exogenously introduced u.v.-damaged reporter plasmids. Taken together our results demonstrate that p21 may modulate the nucleotide excision repair process to facilitate the repair of u.v.-type DNA damage even in the absence of wild-type p53.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sheikh, M., Chen, Y., Smith, M. et al. Role of p21Waf1/Cip1/Sdi1 in cell death and DNA repair as studied using a tetracycline-inducible system in p53-deficient cells. Oncogene 14, 1875–1882 (1997). https://doi.org/10.1038/sj.onc.1201004
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201004
Keywords
This article is cited by
-
Multiple functions of p21 in cancer radiotherapy
Journal of Cancer Research and Clinical Oncology (2021)
-
P21Cip1/WAF1 downregulation is required for efficient PCNA ubiquitination after UV irradiation
Oncogene (2006)
-
Impact of MAPK cascade pathway and P53 pathway upon liver transplant
Journal of Huazhong University of Science and Technology [Medical Sciences] (2005)
-
Cloning and characterization of a novel gene PDRG that is differentially regulated by p53 and ultraviolet radiation
Oncogene (2003)
-
Long-patch base excision repair of apurinic/apyrimidinic site DNA is decreased in mouse embryonic fibroblast cell lines treated with plumbagin: involvement of cyclin-dependent kinase inhibitor p21Waf-1/Cip-1
Oncogene (2002)