Recent Advances in Understanding Werner Syndrome.
Recent Advances in Understanding Werner Syndrome.
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DOI：
10.12688/f1000research.12110.1
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Bohr VA
中科院分区：
文献类型：
--
作者：
Shamanna RA;Croteau DL;Lee JH;Bohr VA
老龄化是一种普遍现象，影响人类健康，是主要疾病病理的主要风险因素。类似于加速衰老的早衰症为理解衰老的特征提供了线索。已知DNA修复基因和端粒酶亚单位的突变会引起早衰样综合征。Werner综合征（WS）是一种常染色体隐性遗传疾病，以加速衰老为特征。定义衰老过程的标志包括基因组不稳定性、端粒磨损、表观遗传改变、蛋白质稳态丧失、营养感测失调、线粒体功能障碍、细胞衰老、干细胞耗竭和细胞间通讯改变。WS概括了衰老的这些特征，并显示出特定癌症的发病率增加和早期发作。基因组的完整性和稳定性确保了细胞的正常功能，主要由DNA修复机制和端粒保护。WRN是RecQ解旋酶，通过调节DNA修复途径和端粒来保护基因组稳定性。WS研究的最新进展已经阐明了WRN在DNA修复途径选择调节、端粒维持、复杂DNA结构的解析、表观遗传调节和干细胞维持中的作用。
Aging, the universal phenomenon, affects human health and is the primary risk factor for major disease pathologies. Progeroid diseases, which mimic aging at an accelerated rate, have provided cues in understanding the hallmarks of aging. Mutations in DNA repair genes as well as in telomerase subunits are known to cause progeroid syndromes. Werner syndrome (WS), which is characterized by accelerated aging, is an autosomal-recessive genetic disorder. Hallmarks that define the aging process include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. WS recapitulates these hallmarks of aging and shows increased incidence and early onset of specific cancers. Genome integrity and stability ensure the normal functioning of the cell and are mainly guarded by the DNA repair machinery and telomeres. WRN, being a RecQ helicase, protects genome stability by regulating DNA repair pathways and telomeres. Recent advances in WS research have elucidated WRN’s role in DNA repair pathway choice regulation, telomere maintenance, resolution of complex DNA structures, epigenetic regulation, and stem cell maintenance.