Genome integrity is essential for life and, as a result, DNA repair systems evolved to remove unavoidable DNA lesions from cellular DNA. Many forms of life possess the capacity to remove interstrand DNA cross-links (ICLs) from their genome but the identity of the naturally-occurring, endogenous substrates that drove the evolution and retention of these DNA repair systems across a wide range of life forms remains uncertain. In this review, we describe more than a dozen chemical processes by which endogenous ICLs plausibly can be introduced into cellular DNA. The majority involve DNA degradation processes that introduce aldehyde residues into the double helix or reactions of DNA with endogenous low molecular weight aldehyde metabolites. A smaller number of the cross-linking processes involve reactions of DNA radicals generated by oxidation.

基因组完整性对于生命至关重要，因此，DNA 修复系统不断进化，以消除细胞 DNA 中不可避免的 DNA 损伤。许多生命形式都具有从基因组中去除链间 DNA 交联 (ICL) 的能力，但驱动这些 DNA 修复系统在多种生命形式中进化和保留的自然发生的内源底物的身份仍然存在。不确定。在这篇综述中，我们描述了十多种化学过程，通过这些过程可以将内源 ICL 引入细胞 DNA。大多数涉及 DNA 降解过程，将醛残基引入双螺旋或 DNA 与内源性低分子量醛代谢物的反应。少数交联过程涉及氧化产生的 DNA 自由基的反应。