TY - JOUR
T1 - Long-patch base excision repair of apurinic/apyrimidinic site DNA is decreased in mouse embryonic fibroblast cell lines treated with plumbagin
T2 - Involvement of cyclin-dependent kinase inhibitor p21Waf-1/Cip-1
AU - Jaiswal, Aruna S.
AU - Bloom, Linda B.
AU - Narayan, Satya
PY - 2002/8/29
Y1 - 2002/8/29
N2 - 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.
AB - 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.
KW - Cell cycle arrest
KW - DNA damage
KW - Long-patch BER
KW - p21
UR - http://www.scopus.com/inward/record.url?scp=0037194607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037194607&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1205789
DO - 10.1038/sj.onc.1205789
M3 - Article
C2 - 12185591
AN - SCOPUS:0037194607
SN - 0950-9232
VL - 21
SP - 5912
EP - 5922
JO - Oncogene
JF - Oncogene
IS - 38
ER -