title: Cell cycle checkpoint control mechanisms that can be disrupted in cancer.
abstract: Maintenance of genomic integrity is essential to avoid cellular transformation, neoplasia, or cell death. DNA synthesis, mitosis, and cytokinesis are important cellular processes required for cell division and the maintenance of cellular homeostasis; they are governed by many extra- and intra-cellular stimuli. Progression of normal cell division depends on cyclin interaction with cyclin-dependent kinases (Cdk) and the degradation of cyclins before chromosomal segregation through ubiquitination. Multiple checkpoints exist and are conserved in the cell cycle in higher eukaryotes to ensure that if one fails, others will take care of genomic integrity and cell survival. Many genes act as either positive or negative regulators of checkpoint function through different kinase cascades, delaying cell cycle progression to repair the DNA lesions and breaks, and assuring equal segregation of chromosomes to daughter cells. Understanding the checkpoint pathways and genes involved in the cellular response to DNA damage and cell division events in normal and cancer cells, provides information about cancer predisposition, and suggests design of small molecules and other strategies for cancer therapy.
authors.affiliation: Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Department of Medicine, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, USA.
authors.forename: Bipin C
authors.initials: BC
authors.lastname: Dash
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D002453:Cell Cycle; D002455:Cell Division; D018385:Centrosome / Q000648:ultrastructure; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D016193:G1 Phase; D016195:G2 Phase; D005838:Genotype; D006801:Humans; D018386:Kinetochores / Q000648:ultrastructure; D008938:Mitosis; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D011418:Prophase; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D015398:Signal Transduction; D008941:Spindle Apparatus; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D004247:DNA; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases