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 language | English |
|---|---|
| Number of pages | 1 |
| Journal | Japanese Journal of Human Genetics |
| Volume | 41 |
| Issue number | 1 |
| Publication status | Published - Dec 1 1996 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Genetics(clinical)
Cite this
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 journal › Article
}
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.
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M3 - Article
AN - SCOPUS:33748168369
VL - 41
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 1
ER -