DNA repair defects and genome instability in Hutchinson-Gilford Progeria Syndrome.
DNA repair defects and genome instability in Hutchinson-Gilford Progeria Syndrome.
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DOI：
10.1016/j.ceb.2015.05.007
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发表时间：
2015-06
影响因子：
7.5
通讯作者：
Kreienkamp R
中科院分区：
文献类型：
--
作者：
Gonzalo S;Kreienkamp R
核层的完整性已成为维持基因组稳定性的重要因素。特别是，编码A型层蛋白（层蛋白A/C）的LMNA基因突变会改变核形态和功能，并导致基因组不稳定。LMNA基因突变与多种退行性疾病和破坏性早衰综合征（如Hutchinson-Gilford Progeria Syndrome， HGPS）和限制性皮肤病（RD）有关。HGPS是一种严重的椎板病，患者在十几岁时死于心肌梗死或中风。HGPS患者来源的细胞表现出核形状异常、表观遗传调控和基因表达改变、端粒缩短、基因组不稳定和过早衰老。本文综述了近年来在确定HGPS病理生理机制方面的最新进展，特别强调了DNA修复缺陷和基因组不稳定性。
The integrity of the nuclear lamina has emerged as an important factor in the maintenance of genome stability. In particular, mutations in the LMNA gene, encoding A-type lamins (lamin A/C), alter nuclear morphology and function, and cause genomic instability. LMNA gene mutations are associated with a variety of degenerative diseases and devastating premature aging syndromes such as Hutchinson-Gilford Progeria Syndrome (HGPS) and Restrictive Dermopathy (RD). HGPS is a severe laminopathy, with patients dying in their teens from myocardial infarction or stroke. HGPS patient-derived cells exhibit nuclear shape abnormalities, changes in epigenetic regulation and gene expression, telomere shortening, genome instability, and premature senescence. This review highlights recent advances in identifying molecular mechanisms that contribute to the pathophysiology of HGPS, with a special emphasis on DNA repair defects and genome instability.