title: Error-promoting DNA synthesis in ovarian cancer cells.
abstract: OBJECTIVE
  The objective of this study is to determine whether an altered DNA replication process is responsible for some of genetic damage observed in ovarian cancer.
  
  
  METHODS
  The replication fidelity of the DNA synthetic process was evaluated in both malignant and non-malignant human ovarian cells. The types of replication errors produced were identified. In addition, kinetic analyses of the efficiency of ovarian cancer DNA polymerases for misincorporating nucleotides were performed.
  
  
  RESULTS
  We report for the first time that ovarian cancer cells harbor an error promoting DNA replication apparatus which contributes to the decrease in DNA synthetic fidelity exhibited by these cells. Our study also shows that the decrease in DNA replication fidelity was not a result of an increased DNA replication activity. In addition, it was observed that the higher rate of DNA replication errors does not result in significant differences in the type of DNA replication-errors made during the DNA replication process; just the relative abundance. A detailed kinetic analysis of the efficiency of misincorporating nucleotides demonstrated that the DNA polymerases within the ovarian cancer cells exhibited a significant propensity for creating purine-pyrimidine nucleotide mismatches relative to non-malignant ovarian cells, while being only slightly more efficient at incorrectly pairing a purine nucleotide with a purine nucleotide.
  
  
  CONCLUSIONS
  All together, these data suggest that the systematic analysis of the DNA replication process in ovarian cancer could uncover information on some of the molecular mechanisms that drive the accumulation of genetic damage, and probably contribute to the pathogenesis of the disease.
authors.affiliation: Indiana University School of Medicine, Department of Medicine, Division of Clinical Pharmacology, USA.
authors.forename: Heqiao
authors.initials: H
authors.lastname: Dai
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hickey
authors.forename: Jianying
authors.initials: J
authors.lastname: Liu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bigsby
authors.forename: Carita
authors.initials: C
authors.lastname: Lanner
authors.forename: Linda H
authors.initials: LH
authors.lastname: Malkas
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D007763:Lac Operon / Q000235:genetics; D009097:Multienzyme Complexes; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D010053:Ovary / Q000166:cytology; D000099272:Replisomes
chemical_list: D004273:DNA, Neoplasm; D004259:DNA-Directed DNA Polymerase; D003838:Deoxyadenine Nucleotides; D009097:Multienzyme Complexes; D000099272:Replisomes; C026600:2'-deoxyadenosine triphosphate
keywords: DNA replication; Multiprotein complex; Ovarian cancer; Replication fidelity