Error-promoting DNA synthesis in ovarian cancer cells

Heqiao Dai, Robert J. Hickey, Jianying Liu, Robert Bigsby, Carita Lanner, Linda H. Malkas

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective. The objective of this study is to determinewhether 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 nonmalignant 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, itwas 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.

Original languageEnglish
Pages (from-to)198-206
Number of pages9
JournalGynecologic Oncology
Volume131
Issue number1
DOIs
StatePublished - Oct 2013

Fingerprint

DNA Replication
Ovarian Neoplasms
DNA
Purine Nucleotides
DNA-Directed DNA Polymerase
Nucleotides
Pyrimidine Nucleotides

Keywords

  • DNA replication
  • Multiprotein complex
  • Ovarian cancer
  • Replication fidelity

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Dai, H., Hickey, R. J., Liu, J., Bigsby, R., Lanner, C., & Malkas, L. H. (2013). Error-promoting DNA synthesis in ovarian cancer cells. Gynecologic Oncology, 131(1), 198-206. https://doi.org/10.1016/j.ygyno.2013.06.022

Error-promoting DNA synthesis in ovarian cancer cells. / Dai, Heqiao; Hickey, Robert J.; Liu, Jianying; Bigsby, Robert; Lanner, Carita; Malkas, Linda H.

In: Gynecologic Oncology, Vol. 131, No. 1, 10.2013, p. 198-206.

Research output: Contribution to journalArticle

Dai, H, Hickey, RJ, Liu, J, Bigsby, R, Lanner, C & Malkas, LH 2013, 'Error-promoting DNA synthesis in ovarian cancer cells', Gynecologic Oncology, vol. 131, no. 1, pp. 198-206. https://doi.org/10.1016/j.ygyno.2013.06.022
Dai, Heqiao ; Hickey, Robert J. ; Liu, Jianying ; Bigsby, Robert ; Lanner, Carita ; Malkas, Linda H. / Error-promoting DNA synthesis in ovarian cancer cells. In: Gynecologic Oncology. 2013 ; Vol. 131, No. 1. pp. 198-206.
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