Universidad Autónoma Metropolitana Unidad Iztapalapa, 186 Avenida San Rafael Atlixco, 09340 Mexico City, DF, Mexico.
Oxid Med Cell Longev. 2012;2012:728430. doi: 10.1155/2012/728430. Epub 2012 Nov 8.
The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life ("health-span"). The DNA mismatch repair system (MMR) is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others.
近年来，由于其在细胞内稳态中的作用，人们对涉及 DNA 修复的机制进行了研究。影响 DNA 完整性的各种有害刺激因素，如遗传序列的改变和基因表达的修饰，会破坏细胞的稳定状态，并对调节细胞凋亡、衰老和癌症的途径产生严重影响。这些改变的途径不仅会改变细胞和生物体的寿命，还会影响生活质量（“健康寿命”）。DNA 错配修复系统（MMR）在物种间高度保守；其在 DNA 完整性的保护中起着至关重要的作用，使其成为延长寿命、衰老和疾病途径研究的必要焦点。在这里，我们回顾了关于 DNA-MMR 功能障碍或缺失及其对细胞内稳态影响的不同见解。特别是，我们将重点介绍由已知修复蛋白 MSH2、MSH6、PMS2 和 MHL1 等调节的 DNA-MMR 机制。
