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Participation of p53 Protein in the Cellular Response to DNA Damage

Publication ,  Journal Article
Kastan, MB; Onyekwere, O; Sidransky, D; Vogelstein, B; Craig, RW
Published in: Cancer Research
January 1, 1991

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 Scholars

Published In

Cancer Research

EISSN

1538-7445

ISSN

0008-5472

Publication Date

January 1, 1991

Volume

51

Start / End Page

6304 / 6311

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B., & Craig, R. W. (1991). Participation of p53 Protein in the Cellular Response to DNA Damage. Cancer Research, 51, 6304–6311.
Kastan, M. B., O. Onyekwere, D. Sidransky, B. Vogelstein, and R. W. Craig. “Participation of p53 Protein in the Cellular Response to DNA Damage.” Cancer Research 51 (January 1, 1991): 6304–11.
Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 Protein in the Cellular Response to DNA Damage. Cancer Research. 1991 Jan 1;51:6304–11.
Kastan, M. B., et al. “Participation of p53 Protein in the Cellular Response to DNA Damage.” Cancer Research, vol. 51, Jan. 1991, pp. 6304–11.
Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 Protein in the Cellular Response to DNA Damage. Cancer Research. 1991 Jan 1;51:6304–6311.

Published In

Cancer Research

EISSN

1538-7445

ISSN

0008-5472

Publication Date

January 1, 1991

Volume

51

Start / End Page

6304 / 6311

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis