The role of primer recognition proteins in DNA replication: Inhibition of cellular proliferation by antisense oligodeoxyribonucleotides

K. D. Kumble, P. L. Iversen, J. K. Vishwanatha

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Primer recognition proteins (PRP) are cofactors for DNA polymerase α and may have a role in lagging-strand DNA replication. PRP is composed of two subunits, which we have previously identified as the protein-tyrosine kinase substrate annexin II and phosphoglycerate kinase (PGK). In this study, we have examined the physiological involvement of these proteins in DNA synthesis and cell proliferation. When exponentially growing human HeLa cells are exposed to antisense phosphorothioate oligodeoxynucleotides to annexin II, ongoing DNA synthesis is reduced. The extent of reduction with antisense oligodeoxynucleotide to PGK was much less than with the antisense annexin II oligodeoxynucleotide. Reductions in the labeling and mitotic indices of HeLa cell cultures are seen after exposure to antisense oligodeoxynucleotides. Flow cytometric analyses indicate that progression from S phase to G2 phase of the cycle is retarded by exposure of cells to the antisense oligodeoxynucleotides. Corresponding sense oligodeoxynucleotides have no inhibitory effects on these parameters. The new synthesis of annexin II and PGK is specifically reduced in the presence of antisense oligodeoxynucleotides, indicating that the complex of newly synthesized annexin II and PGK may participate in PRP function. These experiments indicate that annexin II and PGK may have a physiological role in DNA synthesis and cell cycle progression, and represent the first physiological role for annexin II monomer in cells.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalJournal of Cell Science
Volume101
Issue number1
StatePublished - 1 Jan 1992

Keywords

  • DNA replication
  • Oligodeoxyribonucleotides
  • Primer recognition proteins

Fingerprint Dive into the research topics of 'The role of primer recognition proteins in DNA replication: Inhibition of cellular proliferation by antisense oligodeoxyribonucleotides'. Together they form a unique fingerprint.

  • Cite this