Shamim I. Ahmad
Nottingham Trent University
Nottingham, England

Fumio Hanaoka
Graduate School of Frontier Biosciences, Osaka University
Osaka, Japan

About this Book

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). 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 showes 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.

Table of Contents

1. Historical Aspects of Xeroderma Pigmentosum and Nucleotide Excision Repair
James E. Cleaver

2. Clinical Features of Xeroderma Pigmentosum
Ulrich R. Hengge and Steffen Emmert

3. Xeroderma Pigmentosum and Skin Cancer
Leela Daya‑Grosjean

4. XPA Gene, Its Product and Biological Roles
Ulrike Camenisch and Hanspeter Nägeli

5. XPB and XPD between Transcription and DNA Repair
Brian D. Beck, Dae‑Sik Hah and Suk‑Hee Lee

6. XPC: Its Product and Biological Roles
Kaoru Sugasawa

7. The XPE Gene of Xeroderma Pigmentosum, Its Product and Biological Roles
Drew Bennett and Toshiki Itoh

8. XPF/ERCC4 and ERCC1: Their Products and Biological Roles
Lisa D. McDaniel and Roger A. Schultz

9. XPG: Its Products and Biological Roles
Orlando D. Schärer

10. Xeroderma Pigmentosum Variant, XP‑V: Its Product and Biological Roles
Chikahide Masutani, Fumio Hanaoka and Shamim I. Ahmad

11. Other Proteins Interacting with XP Proteins
Steven M. Shell and Yue Zou

12. The Nucleotide Excision Repair of DNA in Human Cells and Its Association with Xeroderma Pigmentosum
Alexei Gratchev

13. Roles of Oxidative Stress in Xeroderma Pigmentosum
Masaharu Hayashi

14. Xeroderma Pigmentosum: Its Overlap with Trichothiodystrophy, Cockayne Syndrome and Other Progeroid Syndromes
W. Clark Lambert, Claude E. Gagna and Muriel W. Lambert

15. Population Distribution of Xeroderma Pigmentosum
Abdul Manan Bhutto and Sandra H. Kirk

16. Progress and Prospects of Xeroderma Pigmentosum Therapy
Alain Sarasin

17. Animal Models of Xeroderma Pigmentosum
Xue‑Zhi Sun, Rui Zhang, Chun Cui, Yoshi‑Nobu Harada, Setsuji Hisano, Yeunhwa Gu, Yoshihiro Fukui and Hidenori Yonehara