Murdocca Michela, Spitalieri Paola, D'Apice Maria Rosaria, Novelli Giuseppe, Sangiuolo Federica
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Laboratory of Medical Genetics, Tor Vergata Hospital, Rome, Italy.
Mech Ageing Dev. 2023 Apr;211:111790. doi: 10.1016/j.mad.2023.111790. Epub 2023 Feb 9.
Aging is an extremely complex biological process. Aging, cancer and inflammation represent a trinity, object of many interesting researches. The accumulation of DNA damage and its consequences progressively interfere with cellular function and increase susceptibility to developing aging condition. DNA Polymerase delta (Pol δ), encoded by POLD1 gene (MIM#174761) on 19q13.3, is well implicated in many steps of the replication program and repair. Thanks to its exonuclease and polymerase activities, the enzyme is involved in the regulation of the cell cycle, DNA synthesis, and DNA damage repair processes. Damaging variants within the exonuclease domain predispose to cancers, while those occurring in the polymerase active site cause the autosomal dominant Progeroid Syndrome called MDPL, Mandibular hypoplasia, Deafness and Progeroid features with concomitant Lipodystrophy Since DNA damage represents the main cause of ageing and age-related pathologies, an overview of critical Pol δ activities will allow to better understand the associations between DNA damage and nearly every aspect of the ageing process, helping the researchers to counteract all the ageing-pathologies at the same time.
衰老 是一个极其复杂的生物学过程。衰老、癌症和炎症构成了一个三位一体的研究对象，引发了许多有趣的研究。DNA损伤的积累及其后果会逐渐干扰细胞功能，并增加患衰老病症的易感性。DNA聚合酶δ（Pol δ）由位于19q13.3的POLD1基因（MIM#174761）编码，在复制程序和修复的许多步骤中都有重要作用。由于其核酸外切酶和聚合酶活性，该酶参与细胞周期调控、DNA合成以及DNA损伤修复过程。核酸外切酶结构域内的有害变异易引发癌症，而聚合酶活性位点发生的变异则会导致常染色体显性早衰综合征，即MDPL，表现为下颌发育不全、耳聋、早衰特征并伴有脂肪营养不良。由于DNA损伤是衰老及与年龄相关疾病的主要原因，对Pol δ关键活性的概述将有助于更好地理解DNA损伤与衰老过程几乎各个方面之间的关联，帮助研究人员同时对抗所有与衰老相关的疾病。
