Checkpoint Controls and Cancer: Volume 1: Reviews and Model Systems

ISBN-13: 9781617374265 / Angielski / Miękka / 2010 / 318 str.

Axel H. Schonthal; Axel H. Sch Nthal

Opis

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."

Spis treści

Part I. Reviews of Checkpoint Controls, Their Involvement in the Development of Cancer, and Approaches to Their Investigation G1 and S-Phase Checkpoints, Chromosome Instability, and Cancer Hiroshi Nojima Analyzing the G2/M Checkpoint George R. Stark and William R. Taylor Analyzing the Spindle Checkpoint in Yeast and Frogs P. Todd Stukenberg and Daniel J. Burke Cell Cycle Checkpoint Control Mechanisms That Can Be Disrupted in Cancer Bipin C. Dash and Wafik El-Deiry Part II. Analyzing Checkpoint Controls in Diverse Model Systems Establishment of a Cell-Free System to Study the Activation of Chk2 Xingzhi Xu and David F. Stern Analyzing Checkpoint Controls in Human Skin Sandra Pavey and Brian G. Gabrielli Generation and Analysis of Brca1 Conditional Knockout Mice Chu-Xia Deng and Xiaoling Xu Analysis of Cell Cycle Progression and Genomic Integrity in Early Lethal Knockouts Eric J. Brown Xenopus Cell-Free Extracts to Study the DNA Damage Response Vincenzo Costanzo, Kirsten Robertson, and Jean Gautier A Xenopus Cell-Free System for Functional Analysis of the Chfr Ubiquitin Ligase Involved in Control of Mitotic Entry Dongmin Kang, Jim Wong, and Guowei Fang Control of Mitotic Entry After DNA Damage in Drosophila Burnley Jaklevic, Amanda Purdy, and Tin Tin Su Methods for Analyzing Checkpoint Responses in Caenorhabditis elegans Anton Gartner, Amy J. MacQueen, and Anne M. Villeneuve Assaying the Spindle Checkpoint in the Budding Yeast Saccharomyces cerevisiae Christopher M. Yellman and Daniel J. Burke Purification and Analysis of Checkpoint Protein Complexes From Saccharomyces cerevisiae Catherine M. Green and Noel F. Lowndes Index

Blurb

Intracellular checkpoint controls constitute a network of signal transduction pathways that protect cells from external stresses and internal errors by means of cell cycle arrest, DNA repair, or apoptosis. Failure of this machinery can lead to embryonic death, genetic diseases, and cancer. In Checkpoint Controls and Cancer, Volume 1: Reviews and Model Systems, Axel H. Schönthal, PhD, marshals a prestigious panel of researchers working at the cutting edges of their fields to comprehensively review the complexities of checkpoint controls and the model systems available to study them. The authors introduce all of the important components of checkpoint controls, describe their intricate interactions, and highlight the relevance of these processes to the cancer problem. Additional chapters illustrate the advantages of using such diverse model systems as intact human skin, knockout mice, Xenopus, and yeast, and show how they can cross-fertilize and accelerate research both across disciplines and beyond the boundaries of a particular species. A second volume, Activation and Regulation Protocols, provides readily reproducible experimental protocols for studying the molecular components of checkpoint controls and their regulation.
Comprehensive and up-to-date, the two volumes of Checkpoint Controls and Cancer offer novice and experienced researchers alike not only entré into the complexities of this vast field, but also to the full panoply of productive tools needed to deepen understanding of the systems, as well as to develop new and more effective cancer therapies.