The ribonucleotide reductase subunit M2B subcellular localization and functional importance for DNA replication in physiological growth of KB cells

Xiyong Liu, Bingsen Zhou, Lijun Xue, Jennifer Shih, Karen Tye, Christina Qi, Yun Yen

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Ribonucleoside diphosphate reductase (EC 1.17.4.1) (RR) is a potential target for antineoplastic agents due to its crucial role in DNA replication and repair. The expression and activity of RR subunits are highly regulated to maintain an optimal dNTP pool, which is required to maintain genetic fidelity. The human RR small subunit M2B (p53R2) is thought to contribute to DNA repair in response to DNA damage. However, it is not clear whether M2B is involved in providing dNTPs for DNA replication under physiological growth conditions. Serum starvation synchronized studies showed that a rapid increase of M2B was associated with cyclin E, which is responsible for regulation of G 1/S-phase transition. A living cell sorting study that used KB cells in normal growth, further confirmed that M2B increased to maximum levels at the G1/S-phase transition, and decreased with DNA synthesis. Confocal studies revealed that M2B redistributed from the cytoplasm to the nucleus earlier than hRRM2 in response to DNA replication. Nuclear accumulation of M2B is associated with dynamic changes in dNTP at early periods of serum addition. By using M2B-shRNA expression vectors, inhibition of M2B may result in growth retardation in KB cells. We conclude that M2B may translocate from the cytoplasm into the nucleus and allow dNTPs to initiate DNA synthesis in KB cells under physiological conditions. Thus, our findings suggested that M2B might play an important role for initiating DNA replication of KB cells in normal growth.

Original languageEnglish
Pages (from-to)1288-1297
Number of pages10
JournalBiochemical Pharmacology
Volume70
Issue number9
DOIs
Publication statusPublished - Nov 1 2005
Externally publishedYes

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Keywords

  • Cell cycle
  • Cell proliferation
  • DNA replication
  • Ribonucleotide reductase
  • Small interference RNA
  • Subcellular localization

ASJC Scopus subject areas

  • Pharmacology

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