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Control of G1 arrest after DNA damage.
Kastan, M B; Kuerbitz, S J.
Afiliação
  • Kastan MB; Johns Hopkins Oncology Center, Johns Hopkins Hospital, Baltimore, MD 21205.
Environ Health Perspect ; 101 Suppl 5: 55-8, 1993 Dec.
Article em En | MEDLINE | ID: mdl-8013425
ABSTRACT
The temporal relationship between DNA damage and DNA replication may be critical in determining whether the genetic changes necessary for cellular transformation occur after DNA damage. Recent characterization of the mechanisms responsible for alterations in cell-cycle progression after DNA damage in our laboratory have implicated the p53 (tumor suppressor) protein in the G1 arrest that occurs after certain types of DNA damage. In particular, we found that levels of p53 protein increased rapidly and transiently after nonlethal doses of gamma irradiation (XRT) in hematopoietic cells with wild-type, but not mutant, p53 genes. These changes in p53 protein levels were temporally linked to a transient G1 arrest in these cells. Hematopoietic cells with mutant or absent p53 genes did not exhibit this G1 arrest, through they continued to demonstrate a G2 arrest. We recently extended these observations of a tight correlation between the status of the endogenous p53 genes and this G1 arrest after XRT and this cell-cycle alteration after XRT was then established by transfecting cells lacking endogenous p53 genes with a wild-type gene and observing acquisition of the G1 arrest and by transfecting cells processing endogenous wild-type p53 genes with a mutant p53 gene and observing loss of the G1 arrest after XRT. These observations and their significance for our understanding of the mechanisms of DNA damage-induced cellular transformation are discussed.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Fase G1 Limite: Animals / Humans Idioma: En Revista: Environ Health Perspect Ano de publicação: 1993 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Fase G1 Limite: Animals / Humans Idioma: En Revista: Environ Health Perspect Ano de publicação: 1993 Tipo de documento: Article