2003 Fiscal Year Final Research Report Summary
Study of Post-UV DNA Repair Factors for the Prevention from Photodamage of the Skin
| Project/Area Number |
13670877
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
MORWAKI Shinichi Hamamatsu University School of Medicine, Photon Medical Research Center, Associate Professor, 光量子医学研究センター, 助教授 (40303565)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Ultraviolet / DNA repair / Aging / Skin cancer / DNA polymerase δ / fibroblast / Nucleotide Excision Repair / ヌクレオチド除去修復 |
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| Research Abstract |
A reduction in the post-ultraviolet (UV) DNA repair capacity is associated with aging. To clarify the mechanism of this change, we examined the DNA repair capacity of skin fibroblasts from healthy donors of different ages by the two methods: host cell reactivation (HCR) assay and enzyme-linked immunosorbent assay (ELISA) of cyclobutane pyrimidine dimers and pyrimidine-pyrimidone (6-4) photoproducts. In HCR assay, cells from elderly donors exhibited significant declines in the ability to restore transfected reporter DNA damaged by UV light. In contrast, the ability to remove DNA damage declined little with age in ELISA. These results imply that the age-sensitive step took place after the damage excision in nucleotide excision repair (NER). The mRNA expression of DNA repair synthesis-related genes (DNA polymerase d, replication factor C, and proliferating cell nuclear antigen) were markedly decreased in the cells from multiple elderly subjects compared with those from young subjects. Further, the protein level of DNA polymerase d 1, a catalytic subunit of the pivotal factor in repair synthesis, correlated with the mRNA level. These findings suggest that the reduced post-UV DNA repair capacity in aging results from an impairment in the latter step of NER by the decreased expression of factors in repair synthesis.
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[Journal Article] Lehmann AR Two new XPD patients compound heterozygous for the same mutation demonstrate diverse clinical features.
Author(s)
Fujimoto M., Leech SN., Theron T., Fawcett H., Botta E., Mori M., Momoi M., Moriwaki S., Sfefanini M., Nakagawa H., Shuster S., Moss C.
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Journal Title
I Invest Dermatol (in press)
Description
「研究成果報告書概要(欧文)」より
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