DNA interstrand crosslinks (ICLs) covalently connect complementary DNA strands. Consequently, DNA replication and transcription are hampered, DNA damage responses (DDR) are initiated, and cell death is triggered. Therefore, drugs inducing ICLs are effective against rapidly growing cancer cells. However, tumors engage a complicated enzymatic machinery to repair and survive ICLs. Several factors, including the post-translational acetylation/deacetylation of lysine residues within proteins, control this network. Histone deacetylases (HDACs) modulate the expression and functions of DNA repair proteins which remove ICLs and control the accessibility of chromatin. Accordingly, histone deacetylase inhibitors (HDACi) are small, pharmacologically and clinically relevant molecules that sensitize cancer cells to ICL inducers. We discuss the mechanism of ICL repair and targets of HDACi within this pathway.

DNA链间交联（ICL）共价连接互补的DNA链。因此，DNA复制和转录受阻，DNA损伤反应（DDR）启动，并触发细胞死亡。因此，诱导ICL的药物可有效对抗迅速生长的癌细胞。但是，肿瘤会利用复杂的酶促机制修复并存活ICL。几个因素，包括蛋白质中赖氨酸残基的翻译后乙酰化/去乙酰化，控制着这个网络。组蛋白脱乙酰基酶（HDAC）调节DNA修复蛋白的表达和功能，从而去除ICL并控制染色质的可及性。因此，组蛋白脱乙酰基酶抑制剂（HDACi）是小的，药理和临床相关分子，可使癌细胞对ICL诱导剂敏感。