Cell Cycle · 2015 · 18 citations · 29 references
Life SciencesBiochemistryMolecular BiologyDna RepairDna ReplicationMolecular Cell BiologyDna DamageDna Damage SignalingDna Double-strand Break RepairDna Strand BreaksDouble-strand Break RepairNucleotide Excision RepairDeoxynucleoside Triphosphate IncorporationDna Damage Checkpoint KinasesDna Damage Repair PathwaysDna Repair FidelityDna Repair MechanismsDna Repair Pathway RegulationDna Repair PathwaysMacromolecular Complex Formation
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 serum-deprived 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 serum-deprived cells.
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Stimulation of de Novo Pyrimidine Synthesis by Growth Signaling Through mTOR and S6K1
Issam Ben‐Sahra, Jessica J. Howell, John M. Asara et al. · Science · 2013 · 733 citations