Overall Cdk activity modulates the DNA damage response in mammalian cells.
In response to DNA damage, cells activate a phosphorylation-based signaling cascade known as the DNA damage response (DDR). One of the main outcomes of DDR activation is inhibition of cyclin-dependent kinase (Cdk) activity to restrain cell cycle progression until lesions are healed. Recent studies have revealed a reverse connection by which Cdk activity modulates processing of DNA break ends and DDR activation. However, the specific contribution of individual Cdks to this process remains poorly understood. To address this issue, we have examined the DDR in murine cells carrying a defined set of Cdks. Our results reveal that genome maintenance programs of postreplicative cells, including DDR, are regulated by the overall level of Cdk activity and not by specific Cdks.
Cerqueira
Antonio
A
Experimental Oncology Group, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas, E-28029 Madrid, Spain.
Santamaría
David
D
Martínez-Pastor
Bárbara
B
Cuadrado
Miriam
M
Fernández-Capetillo
Oscar
O
Barbacid
Mariano
M
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D056849:Cyclin-Dependent Kinase 3 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D016193:G1 Phase; D016195:G2 Phase; D042822:Genomic Instability; D005838:Genotype; D006657:Histones / Q000378:metabolism; D007399:Interphase; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D016196:S Phase; D013997:Time Factors
D006657:Histones; D047428:Protein Kinase Inhibitors; C475961:gamma-H2AX protein, mouse; D016203:CDC2 Protein Kinase; C495893:Cdk2 protein, mouse; C490914:Cdk3 protein, mouse; C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D056849:Cyclin-Dependent Kinase 3; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases