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

Aruna S. Jaiswal, Linda B. Bloom, Satya Narayan

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Molecular interactions among cell cycle and DNA repair proteins have been described, but the impact of many of these interactions on cell cycle control and DNA repair remains unclear. The cyclin-dependent kinase inhibitor, p21, is known to be involved in DNA damage-induced cell cycle arrest and blocking DNA replication and repair. Participation of p21 has been implicated in nucleotide excision repair. However, the role of p21 in the base excision repair (BER) pathway has not been thoroughly studied. In the present investigation, we treated isogenic mouse embryonic fibroblast (MEF) cell lines containing wild-type (MEF-polβ) or DNA polymerase β (polβ) gene-knockout (MEFpolβKO) with oxidative DNA-damaging agent, plumbagin, and examined its effect on p21 levels and BER activity. Plumbagin treatment caused a S-G2/M phase arrest and cell death of both MEF cell lines, induced p21 levels, and decreased p21-mediated long-patch (LP) BER by blocking DNA ligase activity in the polβ-dependent pathway and by blocking both FEN1 and DNA ligase activity in polβ-independent pathway. These findings suggest that plumbagin induced p21 levels play a regulatory role in cell cycle arrest, apoptosis, and polβ-dependent and -independent LP-BER pathways in MEF cells.

Original languageEnglish (US)
Pages (from-to)5912-5922
Number of pages11
JournalOncogene
Volume21
Issue number38
DOIs
StatePublished - Aug 29 2002
Externally publishedYes

Keywords

  • Cell cycle arrest
  • DNA damage
  • Long-patch BER
  • p21

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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