人体内的细胞常常处于来自环境中的化学物质或者细胞过程中的常规错误带来的不利影响中。虽然这种影响对细胞可以造成损害，但是细胞自身同样可以产生一些应激反应来消除这种损伤。 由美国罗切斯特大学的科学家的组成的一个新的研究小组揭示了一个新的重要机制，当他们处在种种不利因素的影响中时，这种机制可以使细胞识别DNA修复机制，并做好准备，以应对这些损伤对身体带来的威胁。 他们的研究结果发表于最新一期的Science 。 由生物学家Vera Gorbunova和Andrei Seluanov领导的科学小组，主要研究了一种最严重的DNA损伤类型，即DNA双链断裂。 如果不进行修复，这种类型的损坏可能会导致过早衰老和癌症。他们研究了氧化性应激如何影响DNA修复的效率，在正常的细胞活动中会产生一些高活性分子，当身体无法中和这些分子时，氧化性应激便会发生。
该研究小组发现，人体细胞在氧化性应激反应中会合成一种蛋白质，称为SIRT6。增加SIRT6的水平，就能够激发细胞对双链断裂的修复能力。 当用一种药物来处理细胞使SIRT6灭活时，DNA修复才停下来，从而确认了SIRT6在DNA修复的作用。 Gorbunova认为：SIRT6蛋白在结构上与另一种蛋白质SIR2有关，已有证据表明SIR2可以延长多种模式生物的预期寿命。
Gorbunova解释道：“有没有氧化性应激时，SIRT6也影响着DNA的修复，这只是细胞氧化性应激反应放大的效果。”这些细胞对于他们自身拥有的这些资源的使用都很节俭，只有在受到损伤需要修复时，这些修复酶才会发挥作用。SIRT6可能是协调应激反应和DNA修复活动的一个主要调节因子。
SIRT6并不单独行动以修复受损DNA。Gorbunova和他的小组也表明，在应激反应中，SIRT6与一种称为PARP1的蛋白质一起来启动DNA的修复。PARP1是一种酶，它是对DNA损伤做出最早反应的分子之一，与多种DNA修复机制有关。Rochester研究小组还发现，增加SIRT6的水平，细胞能够更迅速地指导DNA修复酶定位于损伤位点，加快对断裂双链的修复。
对于Gorbunova和Seluanov来说，下一步是确定能够增加SIRT6活性的化学激活剂。Gorbunova说 ：一旦有了新的发现，可能会将其研究结果应用于实际的治疗中，以预防某些与衰老有关的疾病的发作。（生物探索译）
生物探索推荐英文原文：
Researchers identify protein that improves DNA repair under stress
Cells in the human body are constantly being exposed to stress from environmental chemicals or errors in routine cellular processes. While stress can cause damage, it can also provide the stimulus for undoing the damage. New research by a team of scientists at the University of Rochester has unveiled an important new mechanism that allows cells to recognize when they are under stress and prime the DNA repair machinery to respond to the threat of damage. Their findings are published in the current issue of Science. The scientists, led by biologists Vera Gorbunova and Andrei Seluanov, focused on the most dangerous type of DNA damage – double strand breaks. Unrepaired, this type of damage can lead to premature aging and cancer. They studied how oxidative stress affects efficiency of DNA repair. Oxidative stress occurs when the body is unable to neutralize the highly-reactive molecules, which are typically produced during routine cellular activities.
The research team found that human cells undergoing oxidative stress synthesized more of a protein called SIRT6. By increasing SIRT6 levels, cells were able to stimulate their ability to repair double strand breaks. When the cells were treated with a drug that inactivated SIRT6, DNA repair came to a halt, thus confirming the role of SIRT6 in DNA repair. Gorbunova notes that the SIRT6 protein is structurally related to another protein, SIR2, which has been shown to extend lifespan in multiple model organisms.
"SIRT6 also affects DNA repair when there is no oxidative stress," explains Gorbunova. "It's just that the effect is magnified when the cells are challenged with even small amounts of oxidative stress." SIRT6 allows the cells to be economical with their resources, priming the repair enzymes only when there is damage that needs to be repaired. Thus SIRT6 may be a master regulator that coordinates stress and DNA repair activities, according to Gorbunova.
SIRT6 does not act alone to repair DNA. Gorbunova and her group also showed that, in response to stress, SIRT6 acts on a protein called PARP1 to initiate DNA repair. PARP1 is an enzyme that is one of the "first responders" to DNA damage and is involved in several DNA repair machineries. By increasing the levels of SIRT6, the Rochester team found that cells were able to more rapidly direct DNA repair enzymes to sites of damage and hasten the repair of double strand breaks.
The next step for Gorbunova and Seluanov is to identify the chemical activators that increase the activity of SIRT6. Once that discovery is made, Gorbunova said it may be possible to apply the results to therapies that prevent the onset of certain aging-related diseases.
