DNA repair defects in stem cell function and aging

被引:127
作者
Park, Y [1 ]
Gerson, SL
机构
[1] Univ Hosp Cleveland, Div Hematol Oncol, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Cleveland, OH 44106 USA
[3] Univ Hosp Cleveland, Ctr Comprehens Canc, Cleveland, OH 44106 USA
[4] Univ Hosp Cleveland, Ctr Stem Cell Regenerat Med, Cleveland, OH 44106 USA
来源
ANNUAL REVIEW OF MEDICINE | 2005年 / 56卷
关键词
DNA repair pathways; hematopoietic stem cells (HSC) transplantation; aplastic anemia;
D O I
10.1146/annurev.med.56.082103.104546
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Cellular DNA is under constant challenge by exogenous and endogenous genotoxic stress, which results in both transient and accumulated DNA damage and genomic instability. All cells are equipped with DNA damage response pathways that trigger DNA repair, cell cycle arrest, and, if need be, apoptosis, to eliminate DNA damage or damaged cells. The consequences of these processes for stem cells can be profound: diminution in stem cell pools, or, because of altered gene expression, an increased chance for stem cell differentiation or malignant transformation. Furthermore, a number of DNA repair abnormalities are linked to premature aging syndromes, and these are associated with defects in the stem cell population. The specific DNA repair systems for which there are data regarding the impact of repair defects on stem cell function include O-6-alkylguanine DNA alkyltransferase, nucleotide excision repair, base excision repair, mismatch repair, non-homologous DNA end-joining Fanconi's anemia protein complex, and homologous recombination. It has recently become clear that deficiencies of these processes are associated not only with cancer and/or aging but also with stem cell defects. This discovery raises the possibility of a link between aging and stem cell dysfunction. In this review, we provide evidence for a link between DNA repair systems and the maintenance and longevity of stem cells.
引用
收藏
页码:495 / 508
页数:14
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