The contribution of CMP kinase to the efficiency of DNA repair

Ning Tsao, Ming Hsiang Lee, Wei Zhang, Yung Chi Cheng, Zee Fen Chang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Cellular supply of deoxynucleoside triphosphates (dNTPs) is crucial for DNA replication and repair. In this study, we investigated the role of CMP/UMP kinase (CMPK), an enzyme catalyzes CDP formation, in DNA repair. Knockdown of CMPK delays DNA repair during recovery from UV damage in serum-deprived cells but not in the cells without serum deprivation. Exogenous supply of cytidine or deoxycytidine facilitates DNA repair dependent on CMPK in serumdeprived cells, suggesting that the synthesis of dCDP or CDP determines the rate of repair. However, CMPK knockdown does not affect the steady state level of dCTP in serum-deprived cells. We then found the localization of CMPK at DNA damage sites and its complex formation with Tip60 and ribonucleotide reductase. Our analysis demonstrated that the N-terminal 32-amino-acid of CMPK is required for its recruitment to DNA damage sites in a Tip60-dependent manner. Re-expression of wild-type but not N-terminus deleted CMPK restores the efficiency of DNA repair in CMPK knockdown cells. We proposed that site-specific dCDP formation via CMPK provides a means to facilitate DNA repair in serumdeprived cells.

Original languageEnglish
Pages (from-to)354-363
Number of pages10
JournalCell Cycle
Volume14
Issue number3
DOIs
StatePublished - Feb 1 2015

Keywords

  • CMP/UMP kinase
  • DNA repair
  • DNTP
  • Recruitment to DNA damage sites
  • Ribonucleotide reductase
  • Serum deprivation
  • Tip60
  • UV irradiation

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