Umfang:
Online-Ressource (digital)
ISBN:
9780387095998
Serie:
Advances in Experimental Medicine and Biology 637
Inhalt:
To understand the molecular mechanisms of XP, XP mouse models have been used, and mice deficient in XPA, XPC, XPD, XPG, XPF, and XPA/CSB have been produced and analysed. A recent elegant technique of targeting gene replacement in mouse embryonic stem cells has provided researchers with the ability to generate mutant mice defective in any specific gene(s). 32 Animals generated in this way display phenotypes and symptoms of XP patients, and have provided valuable tools to understand how and where the deficiency in DNA repair may lead to tumor formation, and also in studies of developmental biology and the aging process. Mouse studies have recently contributed to our understanding of the role of ink4a-Arf in increasing the risk of melanoma photocarcinogenesis in an XPC mutant background. As with many other genetic defects, the distribution of XP globally is not uniform. In most cases the frequency of mutation of a particular trait depends when and where a specific mutation arose, and the longer ago that is, the greater the frequency of mutant in the population unless some selective pressure prevailed. Another factor responsible for the high incidence of any mutation is consanguinity. One of the last chapters analyzes the world distribution of XP and shows that Japan has the highest incidence of XP and of varying complementation groups. After Japan perhaps Egypt suffers most from this inborn error. Here it is also shown that the most common complementation groups are XPA and XPC followed by XPV. XPB and XPE are least frequent. In a recent publication, however, 16 Japanese patients with XPV have been diagnosed and confirmed both clinically and at the cellular level. There is no evidence that interest in XP is waning, and this book should provide both the expert and novice researcher in the field with an excellent overview of the current status of research and pointers to future research goals.
Anmerkung:
Description based upon print version of record
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CONTENTS; 1. HISTORICAL ASPECTS OF XERODERMA PIGMENTOSUM AND NUCLEOTIDE EXCISION REPAIR; Abstract; Historical Aspects; 2. CLINICAL FEATURES OF XERODERMA PIGMENTOSUM; Background; Epidemiology; Dermatological Manifestations; Other Cancers in Xeroderma Pigmentosum; Neurological Manifestations; Ophthalmological Manifestations; Differential Diagnoses; Diagnosis of XP; Management; Prognosis; 3. XERODERMA PIGMENTOSUM AND SKIN CANCER; Abstract; Introduction; XP Genetics and Skin Cancer; Cutaneous Malignancies in XP Patients; The Etiology of XP Skin Cancers and UV Hallmark Mutations
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Tumor Suppressor GenesOncogene Activation in XP Skin Tumors; Modifications of the SHH Signaling Pathway Genes in XP BCC; Impaired Immune Response in XP Patients and Human Papilloma Virus; Conclusions; 4. XPA GENE, ITS PRODUCT AND BIOLOGICAL ROLES; Abstract; Introduction; XPA Gene; XPA Protein and Interactions with Other NER Factors; DNA-Binding Activity of XPA Protein; Recruitment of XPA to Active NER Complexes; Role of XPA-RPA Interactions; How Does XPA Protein Contribute to DNA Damage Recognition?; A Hypothesis for the Mechanism of Damage Verification by XPA
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5. XPB AND XPD BETWEEN TRANSCRIPTION AND DNA REPAIRIntroduction; Structure-Function Relationship; Role in Transcription; Role in NER; Other Roles of XPD; Lessons from Genetic Variations of XPB/XPD; 6. XPC: ITS PRODUCT AND BIOLOGICAL ROLES; Abstract; Introduction; XPC Is a Damage Recognition Factor in GG-NER; Roles for Other Subunits; Ubiquitination and Interaction with UV-DDB; Possible Functions of XPC beyond NER; 7. THE XPE GENE OF XERODERMA PIGMENTOSUM, ITS PRODUCT AND BIOLOGICAL ROLES; Discovery and Background; Expression and Regulation of DDB Protein; Mouse Model; Protein Interactions
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DNA Binding of the DDB ComplexCurrent Models of DDB Function; Conclusion; 8. XPF/ERCC4 AND ERCC1: THEIR PRODUCTS AND BIOLOGICAL ROLES; Introduction; XPF Patients, ERCC4 Mutant CeUs and Gene Cloning; Mouse Models with Relevance to XPF (Erccl and Ercc4); XPF in Nucleotide Excision Repair; ERCC4 in Immunoglobin Switching; ERCC4 in Crosslink Repair; ERCC4 in Telomeres; Summary; 9. XPG: ITS PRODUCTS AND BIOLOGICAL ROLES; Abstract; Introduction; Discovery and Cloning of XPG; Biochemical Properties of the XPG Protein; The Role of XPG in Nucleotide Excision Repair
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Roles of XPG Outside of Nucleotide Excision RepairXP-G Patients and Their Mutant AUeles; XP Group G Patients without CS; Patients with Severe XP and CS Symptoms; XP-G Patients with Late-Onset CS Symptoms; Mouse Models with XPG Deficiency; Conclusion; 10. XERODERMA PIGMENTOSUM VARIANT, XP-V: ITS PRODUCT AND BIOLOGICAL ROLES; Introduction; Human DNA Polymerases; XP-V Gene and Its Homologues; Structure and Activities of Polymerase r; Bypassing of Unusual Nucleotides by Pol r; Mutation in POLH and Its Effects; The Roles of Other Polymerases; Interaction of Pol T with Other Proteins
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Mouse, Plant and Microbial Models for Pol r
Weitere Ausg.:
ISBN 9780387095981
Weitere Ausg.:
Buchausg. u.d.T. ISBN 9780387095981
Sprache:
Englisch
Fachgebiete:
Biologie
DOI:
10.1007/978-0-387-09599-8
URL:
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