ABSTRACT Progeroid syndromes induced by mutations in lamin A or in its interactors – named progeroid laminopathies – are model systems for the dissection of the molecular pathways causing physiological and premature aging. A large amount of data, based mainly on the Hutchinson Gilford Progeria syndrome (HGPS), one of the best characterized progeroid laminopathy, has highlighted the role of lamins in multiple DNA activities, including replication, repair, chromatin organization and telomere function. On the other hand, the phenotypes generated by mutations affecting genes directly acting on DNA function, as mutations in the helicases WRN and BLM or in the polymerase polδ, share many of the traits of progeroid laminopathies. These evidences support the hypothesis of a concerted implication of DNA function and lamins in aging. We focus here on these aspects to contribute to the comprehension of the driving forces acting in progeroid syndromes and premature aging.

中文翻译：

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早衰综合征中的基因组不稳定性和 DNA 复制缺陷

摘要 由 lamin A 或其相互作用物突变引起的早衰综合征 - 称为早老性椎板病 - 是解剖导致生理和过早衰老的分子途径的模型系统。大量数据主要基于 Hutchinson Gilford Progeria 综合征 (HGPS)，这是特征最好的早老性椎板病之一，强调了 lamin 在多种 DNA 活动中的作用，包括复制、修复、染色质组织和端粒功能。另一方面，由影响直接作用于 DNA 功能的基因的突变产生的表型，如解旋酶 WRN 和 BLM 或聚合酶 polδ 中的突变，具有早老性椎板病的许多特征。这些证据支持 DNA 功能和核纤层蛋白在衰老过程中协同作用的假设。