Endogenous DNA damage and its repair during haematopoiesis

内源性DNA损伤是所有生物体中突变积累的重要和主要原因。这可以在与从老年动物和大多数癌症中获得的细胞相关的突变签名中看到。已确定的引起内源性DNA损伤的因素和过程是氧气、水、结构DNA和DNA复制和转录。然而，一个根本的问题是，是否有其他因素是内源性DNA损伤的普遍驱动因素，以及DNA修复途径是否缓解了这种损伤。我们的研究已经证实，在我们的细胞中会产生简单的醛，如甲醛和乙醛，它们可能通过形成DNA交联链而导致DNA损伤。我们发现，两层保护机制(乙醛解毒和DNA修复)确保这些代谢物不会造成DNA损伤和突变。

Endogenous DNA damage is an important and dominant cause for the accumulation of mutations in all organisms. This can be seen in the mutation signatures associated with cells obtained from aged animals and in most cancers. The established factors and processes that cause endogenous DNA damage are oxygen, water, structured DNA and DNA replication and transcription. However, a fundamental question is whether there are other factors that are prevalent drivers for endogenous DNA damage and DNA repair pathways mitigate against such damage. Our research has identified that simple aldehydes such as formaldehyde and acetaldehyde are produced in our cells that can cause DNA damage possibly through the formation of DNA crosslinks. We uncovered that a two-tier protection mechanism (aldehyde detoxification and DNA repair) ensure that these metabolites do not cause DNA damage and mutations.