Description
Humana Press Inc. Checkpoint Controls And Cancer Vol.2: Activation And Regulation Protocols by Axel H. Schoenthal
Intracellular Checkpoint Controls Constitute A Network Of Signal Transd- Tion Pathways That Protect Cells From External Stresses And Internal Errors. Ext- Nal Stresses Can Be Generated By The Continuous Assault Of Dna-Damaging Agents Such As Environmental Mutagens Ultraviolet (Uv) Light Ionizing Radiation Or The Reactive Oxygen Species That Can Arise During Normal Cellular Metabolism. In Response To Any Of These Assaults On The Integrity Of The Genome The Activation Of The Network Of Checkpoint Control Pathways Can Lead To Diverse Cellular Responses Such As Cell Cycle Arrest Dna Repair Or Elimination Of The Cell By Cell Death (Apoptosis) If The Damage Cannot Be Repaired. Moreover Internal Errors Can Occur During The Highly Orchestrated Replication Of The Cellular Genome And Its Distribution Into Daughter Cells. Here The Temporal Order Of These Cell Cycle Events Must Be Strictly Enforced-For Example To Ensure That Dna Replication Is C- Plete And Occurs Only Once Before Cell Division Or To Monitor Mitotic Spindle Assembly And To Prevent Exit From Mitosis Until Chromosome Segregation Has Been Completed. Thus Well Functioning Checkpoint Mechanisms Are Central To The Maintenance Of Genomic Integrity And The Basic Viability Of Cells And The- Fore Are Essential For Proper Development And Survival. The Importance Of Proper Functioning Of Checkpoints Becomes Plainly Obvious Under Conditions In Which This Control Network Malfunctions And Fails. Depending On The Severity And Timing Failure Of This Machinery Can Lead To Embryonic Lethality Genetic Diseases And Cancer.