title: [Cell cycle, mitosis and therapeutic applications].
abstract: Genomic DNA is constantly under stress of endogenous and exogenous DNA damaging agents. Without proper care, the DNA damage causes an alteration of the genomic structure and can lead to cell death or the occurrence of mutations involved in tumorigenesis. During the process of evolution, organisms have acquired a series of response mechanisms and repair of DNA damage, thereby ensuring the maintenance of genome stability and faithful transmission of genetic information. The checkpoints are the major mechanisms by which a cell can respond to DNA damage, either by actively stopping the cell cycle or by induction of apoptosis. Two parallel signalling pathways, ATM and ATR respond to genotoxic stress by activating their downstream target proteins including the two effectors kinases CHK1 and CHK2. Promising preliminary data render these proteins potential targets for therapeutic development against cancer.
authors.affiliation: Institut Gustave-Roussy, service de radiothérapie oncologie, université Paris-XI, Villejuif, France. s.lheureux@baclesse.fr
authors.forename: Antonin
authors.initials: A
authors.lastname: Levy
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges-Sauvin
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
mesh_terms: D000782:Aneuploidy; D017209:Apoptosis / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D004789:Enzyme Activation; D042822:Genomic Instability; D006801:Humans; D007399:Interphase / Q000502:physiology; D008938:Mitosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases