Eukaryotic DNA Damage Surveillance and Repair / Edition 1

by Keith William Caldecott

Overview

Eukaryotic DNA Damage Surveillance and Repair contains chapters from experts in the field of DNA damage detection, repair, and cell cycle control. The work reviews current understanding of how different types of DNA damage are detected and focuses on how these surveillance mechanisms are coupled to processes of DNA repair, cell cycle control, and apoptosis.

The title will be of interest to undergraduate/postgraduate students and academics alike.

Product Details

ISBN-13:	9780306479878
Publisher:	Springer US
Publication date:	05/31/2004
Series:	Molecular Biology Intelligence Unit
Edition description:	2004
Pages:	161
Product dimensions:	6.10(w) x 9.25(h) x 0.03(d)

Table of Contents

	Preface	vii
1.	DNA Damage Surveillance in Saccharomyces cerevisiae	1
	Introduction	1
	Sensing DNA Damage: A Complex Problem	4
	From Checkpoint Genes to Protein Complexes	6
	The Rad24 Epistasis Group: RFC-Like and PCNA-Like Complexes	7
	Mec1/Ddc2: Signal Transduction and More	10
	The Mre11 Complex: DSBs and Checkpoint Signalling	12
	The S Phase Checkpoint	15
	Checkpoints and Genome Surveillance	16
	Focal Recruitment of Checkpoint and Repair Complexes to Damage Sites	17
	The Chromatin Connection	18
	Concluding Remarks	20
2.	Mammalian Base Excision Repair	27
	Abstract	27
	Introduction	27
	Base Excision Repair Proteins	28
	Coordination of Base Excision Repair	36
3.	Detection and Repair of DNA Single-Strand Breaks	49
	Abstract	49
	The Origin and Structure of DNA Single-Strand Breaks	49
	The Threat of Single-Strand Breaks to Genetic Stability and Cell Death	50
	Polypeptides Involved in DNA Single-Strand Break Repair	50
	PARP-1, XRCC1 and the Detection of SSBs	50
	AP Endonuclease-1 (APE1)	53
	Polynucleotide Kinase (PNK)	54
	DNA Polymerase-[beta] (Pol[beta])	54
	DNA Ligase III	55
	SSBR Protein Complexes; Pre-Formed or Assembled at Breaks?	56
	SSBR Pathways and the Cell Cycle	57
4.	The Detection and Repair of Nucleotide Damage and Coupling to Major Cellular Regulatory Processes in Mammalian Cells	63
	Abstract	63
	Introduction	63
	Types of Damage Repaired by NER	66
	Recognition of Damage in Nontranscribing Regions of the Genome	67
	Recognition of Damage in Transcriptionally Active Regions of the Genome	68
	The Core Excision Process Common to GGR and TCR	70
	Ubiquitination and Proteolysis in DNA Repair	73
	Inducible Responses to UV Irradiation	74
	Kinase Activation and Cellular Response to UV Damage	75
	Replication of Damaged DNA	76
	Differentiation and Tissue-Specific Expression of DNA Repair Genes	78
	Polymorphisms in DNA Repair Genes	78
5.	Mammalian DNA Mismatch Repair	90
	Abstract	90
	What Is DNA Mismatch Repair	90
	The Mismatch Repair Mechanism	91
	The Mismatch Repair Proteins	93
	The MutS Homolog Proteins	96
	Proteins That Interact with the MuL and MutS Homologues	98
	Apoptosis and Drug Resistance	101
	MMR and Apoptotic Pathways	102
	Conclusions	103
6.	Origin, Recognition, Signaling and Repair of DNA Double-Strand Breaks in Mammalian Cells	107
	Abstract	107
	Replication-Independent Double-Strand Breaks (DSBs)	108
	Replication Associated DSBs (One-Sided Breaks)	121
7.	The Mechanism of DNA Non-Homologous End-Joining: Lessons Learned from Biophysical, Biochemical and Cellular Studies	146
	Abstract	146
	Introduction	146
	Nature of the DNA Ends to Be Rejoined	147
	Structure and Biochemical Analysis of the Core NHEJ Proteins	148
	Additional Proteins Implicated in DNA NHEJ	150
	Further Proteins Interacting with Core NHEJ Components	151
	Model for NHEJ and Potential Additional Interacting Proteins	152
	Index	159