In vitro and in vivo analysis of the XPA gene

Kiyoji Tanaka, Yoshimichi Nakatsu, Masafumi Saijo, Takehiro Kobayashi, Toshiro Matsuda, Isao Kuraoka, Hiroaki Murai, Hironobu Nakane, Seiji Takeuchi, Naohiko Kodo, Masahiko Nitta

Research output: Contribution to journalArticle

Abstract

Nucleotide excision repair (NER) is a versatile repair system capable of rectifying a broad spectrum of DNA damage. The importance of NER has been suggested by studies of the human inherited disease, xeroderma pigmentosum (XP), which is characterized by a high incidence of skin cancer in sun-exposed areas. Cells from XP patients are hypersensitive to killing by UVirradiation and have a defect in the early steps of NER processes. There are seven different complementation groups (groups A through G) in XP. We examined the roles of the group A XP (XPA) gene and its product in NER and prevention of carcinogen-induced tumorigenesis. The XPA gene encodes a protein of 273 amino acids with C4 type zinc finger motif, and the XPA protein preferentially bound to DNA damaged by UV, cisplatin or osmium tetroxide, indicating that the XPA protein is involved in the damage recognition step of NER processes. Moreover, the XPA protein has an ability to interact with other proteins. We found that the 34 kDa subunit of replication protein A (RPA) and DNA repair protein ERCC1 bound to the XPA protein. Biological significance of these interactions will be discussed. To elucidate the in vivo function of the XPA gene and molecular basis of group A XP phenotype, we established X/M-deficient mice using mouse ES cell techniques. The XPAdeficient mice were defective in NER process and highly susceptible to UV-induced tumorigenesis. The X/M-deficient mice provide a good in vivo model to study UV-induced skin carcinogenesis in group A XP patients.

Original languageEnglish
Number of pages1
JournalJapanese Journal of Human Genetics
Volume41
Issue number1
Publication statusPublished - Dec 1 1996
Externally publishedYes

Fingerprint

Xeroderma Pigmentosum
DNA Repair
Genes
Proteins
Carcinogenesis
Replication Protein A
Osmium Tetroxide
Zinc Fingers
Skin Neoplasms
Solar System
In Vitro Techniques
Carcinogens
Cisplatin
DNA Damage
Phenotype
Amino Acids
Skin
DNA
Incidence

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

Tanaka, K., Nakatsu, Y., Saijo, M., Kobayashi, T., Matsuda, T., Kuraoka, I., ... Nitta, M. (1996). In vitro and in vivo analysis of the XPA gene. Japanese Journal of Human Genetics, 41(1).

In vitro and in vivo analysis of the XPA gene. / Tanaka, Kiyoji; Nakatsu, Yoshimichi; Saijo, Masafumi; Kobayashi, Takehiro; Matsuda, Toshiro; Kuraoka, Isao; Murai, Hiroaki; Nakane, Hironobu; Takeuchi, Seiji; Kodo, Naohiko; Nitta, Masahiko.

In: Japanese Journal of Human Genetics, Vol. 41, No. 1, 01.12.1996.

Research output: Contribution to journalArticle

Tanaka, K, Nakatsu, Y, Saijo, M, Kobayashi, T, Matsuda, T, Kuraoka, I, Murai, H, Nakane, H, Takeuchi, S, Kodo, N & Nitta, M 1996, 'In vitro and in vivo analysis of the XPA gene', Japanese Journal of Human Genetics, vol. 41, no. 1.
Tanaka K, Nakatsu Y, Saijo M, Kobayashi T, Matsuda T, Kuraoka I et al. In vitro and in vivo analysis of the XPA gene. Japanese Journal of Human Genetics. 1996 Dec 1;41(1).
Tanaka, Kiyoji ; Nakatsu, Yoshimichi ; Saijo, Masafumi ; Kobayashi, Takehiro ; Matsuda, Toshiro ; Kuraoka, Isao ; Murai, Hiroaki ; Nakane, Hironobu ; Takeuchi, Seiji ; Kodo, Naohiko ; Nitta, Masahiko. / In vitro and in vivo analysis of the XPA gene. In: Japanese Journal of Human Genetics. 1996 ; Vol. 41, No. 1.
@article{ed49549ae2464ea4bcebe74e9c30227d,
title = "In vitro and in vivo analysis of the XPA gene",
abstract = "Nucleotide excision repair (NER) is a versatile repair system capable of rectifying a broad spectrum of DNA damage. The importance of NER has been suggested by studies of the human inherited disease, xeroderma pigmentosum (XP), which is characterized by a high incidence of skin cancer in sun-exposed areas. Cells from XP patients are hypersensitive to killing by UVirradiation and have a defect in the early steps of NER processes. There are seven different complementation groups (groups A through G) in XP. We examined the roles of the group A XP (XPA) gene and its product in NER and prevention of carcinogen-induced tumorigenesis. The XPA gene encodes a protein of 273 amino acids with C4 type zinc finger motif, and the XPA protein preferentially bound to DNA damaged by UV, cisplatin or osmium tetroxide, indicating that the XPA protein is involved in the damage recognition step of NER processes. Moreover, the XPA protein has an ability to interact with other proteins. We found that the 34 kDa subunit of replication protein A (RPA) and DNA repair protein ERCC1 bound to the XPA protein. Biological significance of these interactions will be discussed. To elucidate the in vivo function of the XPA gene and molecular basis of group A XP phenotype, we established X/M-deficient mice using mouse ES cell techniques. The XPAdeficient mice were defective in NER process and highly susceptible to UV-induced tumorigenesis. The X/M-deficient mice provide a good in vivo model to study UV-induced skin carcinogenesis in group A XP patients.",
author = "Kiyoji Tanaka and Yoshimichi Nakatsu and Masafumi Saijo and Takehiro Kobayashi and Toshiro Matsuda and Isao Kuraoka and Hiroaki Murai and Hironobu Nakane and Seiji Takeuchi and Naohiko Kodo and Masahiko Nitta",
year = "1996",
month = "12",
day = "1",
language = "English",
volume = "41",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - In vitro and in vivo analysis of the XPA gene

AU - Tanaka, Kiyoji

AU - Nakatsu, Yoshimichi

AU - Saijo, Masafumi

AU - Kobayashi, Takehiro

AU - Matsuda, Toshiro

AU - Kuraoka, Isao

AU - Murai, Hiroaki

AU - Nakane, Hironobu

AU - Takeuchi, Seiji

AU - Kodo, Naohiko

AU - Nitta, Masahiko

PY - 1996/12/1

Y1 - 1996/12/1

N2 - Nucleotide excision repair (NER) is a versatile repair system capable of rectifying a broad spectrum of DNA damage. The importance of NER has been suggested by studies of the human inherited disease, xeroderma pigmentosum (XP), which is characterized by a high incidence of skin cancer in sun-exposed areas. Cells from XP patients are hypersensitive to killing by UVirradiation and have a defect in the early steps of NER processes. There are seven different complementation groups (groups A through G) in XP. We examined the roles of the group A XP (XPA) gene and its product in NER and prevention of carcinogen-induced tumorigenesis. The XPA gene encodes a protein of 273 amino acids with C4 type zinc finger motif, and the XPA protein preferentially bound to DNA damaged by UV, cisplatin or osmium tetroxide, indicating that the XPA protein is involved in the damage recognition step of NER processes. Moreover, the XPA protein has an ability to interact with other proteins. We found that the 34 kDa subunit of replication protein A (RPA) and DNA repair protein ERCC1 bound to the XPA protein. Biological significance of these interactions will be discussed. To elucidate the in vivo function of the XPA gene and molecular basis of group A XP phenotype, we established X/M-deficient mice using mouse ES cell techniques. The XPAdeficient mice were defective in NER process and highly susceptible to UV-induced tumorigenesis. The X/M-deficient mice provide a good in vivo model to study UV-induced skin carcinogenesis in group A XP patients.

AB - Nucleotide excision repair (NER) is a versatile repair system capable of rectifying a broad spectrum of DNA damage. The importance of NER has been suggested by studies of the human inherited disease, xeroderma pigmentosum (XP), which is characterized by a high incidence of skin cancer in sun-exposed areas. Cells from XP patients are hypersensitive to killing by UVirradiation and have a defect in the early steps of NER processes. There are seven different complementation groups (groups A through G) in XP. We examined the roles of the group A XP (XPA) gene and its product in NER and prevention of carcinogen-induced tumorigenesis. The XPA gene encodes a protein of 273 amino acids with C4 type zinc finger motif, and the XPA protein preferentially bound to DNA damaged by UV, cisplatin or osmium tetroxide, indicating that the XPA protein is involved in the damage recognition step of NER processes. Moreover, the XPA protein has an ability to interact with other proteins. We found that the 34 kDa subunit of replication protein A (RPA) and DNA repair protein ERCC1 bound to the XPA protein. Biological significance of these interactions will be discussed. To elucidate the in vivo function of the XPA gene and molecular basis of group A XP phenotype, we established X/M-deficient mice using mouse ES cell techniques. The XPAdeficient mice were defective in NER process and highly susceptible to UV-induced tumorigenesis. The X/M-deficient mice provide a good in vivo model to study UV-induced skin carcinogenesis in group A XP patients.

UR - http://www.scopus.com/inward/record.url?scp=33748168369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748168369&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33748168369

VL - 41

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 1

ER -