Disruption of the mevalonate pathway induces dNTP depletion and DNA damage
Sánchez C, Martín J, Jin JS, Dávalos A, Zhang W, de la Peña G, Martínez-Botas J, Rodríguez-Acebes S, Suárez Y, Hazen MJ, Gómez-Coronado D, Busto R, Cheng YC, Lasunción MA. Disruption of the mevalonate pathway induces dNTP depletion and DNA damage. Biochimica Et Biophysica Acta 2015, 1851: 1240-1253. PMID: 26055626, DOI: 10.1016/j.bbalip.2015.06.001.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateCarboxy-LyasesCell Cycle CheckpointsCell Line, TumorCell ProliferationCheckpoint Kinase 1DeoxyribonucleosidesDNA DamageDNA ReplicationGene Expression RegulationHalogenationHemiterpenesHistonesHL-60 CellsHumansLymphocytesMevalonic AcidOrganophosphorus CompoundsProtein KinasesRNA, Small InterferingSignal TransductionConceptsMevalonate diphosphate decarboxylaseDiphosphate decarboxylaseCell cycle progressionDNA replicationCycle progressionMevalonate pathwayDNA damageDNA damage responseNon-sterol isoprenoidsCell proliferationInhibition of Chk1Cholesterol biosynthesis pathwayMassive cell deathSubsequent DNA damageΓ-H2AX formationCell cycle arrestReplication stressBiosynthesis pathwayΓ-H2AX fociChk1 activationDamage responseIsopentenyl diphosphateMitosis completionCell divisionDNTP depletion