Mechanisms and implications of the age-associated decrease in DNA repair capacity

被引：165

作者：

Goukassian, D ^{[1
]}

Gad, F ^{[1
]}

Yaar, M ^{[1
]}

Eller, MS ^{[1
]}

Nehal, US ^{[1
]}

Gilchrest, BA ^{[1
]}

机构：

[1] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA

来源：

FASEB JOURNAL | 2000年 / 14卷 / 10期

关键词：

aging; DNA damage repair; DNA photoproducts; nucleotide excision repair;

D O I：

10.1096/fj.14.10.1325

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Skin cancer incidence is clearly linked to UV irradiation and increases exponentially with age, We studied the rate of removal of thymine dimers and (6-4) photoproducts in UV-irradiated human dermal fibroblasts derived from donors of different ages. There was a significant decrease with aging in the repair rates of both thymine dimers and (6-4) photoproducts. (P<0.001). In addition, there was an age-associated decrease in the protein levels of ERCC3, PCNA, RPA, XPA, and p53 that participate in nucleotide excision repair. Moreover, the mRNA levels of XPA, ERCC3, and PCNA were significantly reduced with aging, suggesting that these decreases are often regulated at the mRNA level. Furthermore, with age induction of p53 after UV irradiation was significantly reduced. Taken together, our data suggest that the age-associated decrease in the repair of UV-induced DNA damage results at least in part from decreased levels of proteins that participate in the repair process.

引用

页码：1325 / 1334

页数：10

共 96 条

[81] THE P21 INHIBITOR OF CYCLIN-DEPENDENT KINASES CONTROLS DNA-REPLICATION BY INTERACTION WITH PCNA [J].