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Regulatory roles of p21 and apurinic/apyrimidinic endonuclease 1 in base excision repair.
Tom, S; Ranalli, T A; Podust, V N; Bambara, R A.
Afiliação
  • Tom S; Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
J Biol Chem ; 276(52): 48781-9, 2001 Dec 28.
Article em En | MEDLINE | ID: mdl-11641413
ABSTRACT
Many types of DNA damage induce a cellular response that inhibits replication but allows repair by up-regulating the p53 pathway and inducing p21(Cip1, Waf1, Sdi1). The p21 regulatory protein can bind proliferating cell nuclear antigen (PCNA) and prohibit DNA replication. We show here that p21 also inhibits PCNA stimulation of long patch base excision repair (BER) in vitro. p21 disrupts PCNA-directed stimulation of flap endonuclease 1 (FEN1), DNA ligase I, and DNA polymerase delta. The dilemma is to understand how p21 prevents DNA replication but allows BER in vivo. Differential regulation by p21 is likely to relate to the utilization of DNA polymerase beta, which is not sensitive to p21, in the repair pathway. We have also found that apurinic/apyrimidinic endonuclease 1 (APE1) stimulates long patch BER. Furthermore, neither APE1 activity nor its ability to stimulate long patch BER is significantly affected by p21 in vitro. We propose that APE1 serves as an assembly and coordination factor for long patch BER proteins. APE1 initially cleaves the DNA and then facilitates the sequential binding and catalysis by DNA polymerase beta, DNA polymerase delta, FEN1, and DNA ligase I. This model implies that BER can be regulated differentially, based upon the assembly of relevant proteins around APE1 in the presence or absence of PCNA.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ciclinas / Antígeno Nuclear de Célula em Proliferação / Carbono-Oxigênio Liases / Reparo do DNA / Inibidores Enzimáticos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2001 Tipo de documento: Article
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ciclinas / Antígeno Nuclear de Célula em Proliferação / Carbono-Oxigênio Liases / Reparo do DNA / Inibidores Enzimáticos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2001 Tipo de documento: Article