Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1374, Sao Paulo, SP, Brazil.
Front Biosci (Landmark Ed). 2012 Jan 1;17(4):1362-88. doi: 10.2741/3992.
Human cells are constantly exposed to DNA damage. Without repair, damage can result in genetic instability and eventually cancer. The strong association between the lack of DNA damage repair, mutations and cancer is dramatically demonstrated by a number of cancer-prone human syndromes, such as xeroderma pigmentosum (XP), ataxia-telangiectasia (AT) and Fanconi anemia (FA). This review focuses on the historical discoveries related with these three diseases and describes their impact on the understanding of DNA repair mechanisms and the causes of human cancer. As deficiencies in DNA repair are also often related with progeria symptoms, unrepaired damage and aging are somehow related. Several other pathologies associated with DNA repair defects, genetic instability and increased cancer risk are also discussed. In fact, studies with cells from these many syndromes have helped in understanding important levels of protection against cancer and aging, although little help has actually been conferred to the patients in terms of therapy. Finally, the recent advances in combined basic and translational research on DNA repair and chemotherapy are presented.
人类细胞不断受到 DNA 损伤的影响。如果不加以修复，损伤可能导致遗传不稳定性，最终导致癌症。一些易患癌症的人类综合征，如着色性干皮病 (XP)、共济失调毛细血管扩张症 (AT) 和范可尼贫血 (FA)，强烈表明缺乏 DNA 损伤修复、突变和癌症之间存在关联。本综述重点介绍了与这三种疾病相关的历史发现，并描述了它们对理解 DNA 修复机制和人类癌症原因的影响。由于 DNA 修复的缺陷也常与早衰症状有关，因此未修复的损伤和衰老在某种程度上是相关的。还讨论了其他一些与 DNA 修复缺陷、遗传不稳定性和癌症风险增加相关的病理学。事实上，来自这些多种综合征的细胞研究有助于了解预防癌症和衰老的重要层面，尽管在治疗方面实际上并没有给患者带来多少帮助。最后，介绍了 DNA 修复和化疗的基础和转化研究的最新进展。
