Radiation and Cancer Biology Division, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Cell Cycle. 2009 Dec;8(23):3860-5. doi: 10.4161/cc.8.23.10092. Epub 2009 Dec 15.
Research performed in the last few years has revealed important roles for the spatial and temporal organization of the genome on genome function and integrity. A challenge in the field is to determine the molecular mechanisms involved in the organization of genome function. A-type lamins, key structural components of the nucleus, have been implicated in the maintenance of nuclear architecture and chromatin structure. Interestingly, alterations of A-type lamins lead to defects in DNA replication and repair as well as gene transcription and silencing. Elucidating the functions of these proteins is a topical subject since alterations of A-type lamins are associated with a variety of human diseases, ranging from muscular dystrophies and premature aging syndromes to cancer. Here, we discuss novels roles for A-type lamins in the maintenance of telomere structure, length and function as well as in the stabilization of a key DNA damage response factor. These studies support the notion that increased genomic instability due to defects in telomere biology and DNA repair contribute to the pathogenesis of lamin-related diseases.
近年来的研究揭示了基因组在基因组功能和完整性方面的空间和时间组织的重要作用。该领域的一个挑战是确定参与基因组功能组织的分子机制。A 型核纤层蛋白是核的关键结构成分，与核架构和染色质结构的维持有关。有趣的是，A 型核纤层蛋白的改变导致 DNA 复制和修复以及基因转录和沉默的缺陷。阐明这些蛋白质的功能是一个热门话题，因为 A 型核纤层蛋白的改变与多种人类疾病有关，从肌肉萎缩症和早衰综合征到癌症。在这里，我们讨论了 A 型核纤层蛋白在维持端粒结构、长度和功能以及稳定关键的 DNA 损伤反应因子方面的新作用。这些研究支持这样一种观点，即由于端粒生物学和 DNA 修复缺陷导致的基因组不稳定性增加，导致与核纤层蛋白相关疾病的发病机制。
