Participation of p53 Protein in the Cellular Response to DNA Damage

Published

Journal Article

The inhibition of replicative DNA synthesis that follows DNA damage may be critical for avoiding genetic lesions that could contribute to cellular transformation. Exposure of MI -1 myeloblastic leukemia cells to nonlethal doses of the DNA damaging agents, -»-irradiationor actinomycin D, causes a transient inhibition of replicative DNA synthesis via both (., and (F. arrests. Levels of p53 protein in MI -I cells and in proliferating normal bone marrow myeloid progenitor cells increase and decrease in temporal association with the Gãarrest. In contrast, the S-phase arrest of MI -1 cells caused by exposure to the anti-metabolite, cytosino arabinoside, which does not directly damage DNA, is not associated with a significant change in p53 protein levels. Caffeine treatment blocks both the (F, arrest and the induction of p53 protein after f-irradiation, thus suggesting that blocking the induction of pS3 protein may contribute to the previously observed effects of caffeine on cell cycle changes after DNA damage. Unlike MI -I cells and normal bone marrow myeloid progenitor cells, hematopoietic cells that either lack p53 gene expression or overexpress a mutant form of the pS3 gene do not exhibit a (., arrest after -y-irradiation; however, the G2 arrest is unaffected by the status of the p53 gene. These results suggest a role for the wild-type pS3 protein in the inhibition of DNA synthesis that follows DNA damage and thus suggest a new mechanism for how the loss of wild-type p53 might contribute to tumorigenesis. © 1991, American Association for Cancer Research. All rights reserved.

Duke Authors

Cited Authors

  • Kastan, MB; Onyekwere, O; Sidransky, D; Vogelstein, B; Craig, RW

Published Date

  • January 1, 1991

Published In

Volume / Issue

  • 51 /

Start / End Page

  • 6304 - 6311

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Citation Source

  • Scopus