Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Trends Biochem Sci. 2010 May;35(5):247-52. doi: 10.1016/j.tibs.2010.01.003. Epub 2010 Feb 19.
DNA interstrand crosslinks (ICLs) can arise from reactions with endogenous chemicals, such as malondialdehyde - a lipid peroxidation product - or from exposure to various clinical anti-cancer drugs, most notably bifunctional alkylators and platinum compounds. Because they covalently link the two strands of DNA, ICLs completely block transcription and replication, and, as a result, are lethal to the cell. It is well established that proteins that function in nucleotide excision repair and homologous recombination are involved in ICL resolution. Recent work, coupled with a much earlier report, now suggest an emerging link between proteins of the base excision repair pathway and crosslink processing.
DNA 链间交联 (ICLs) 可由与内源性化学物质的反应产生,例如丙二醛——一种脂质过氧化产物——或由暴露于各种临床抗癌药物引起,尤其是双功能烷化剂和铂化合物。因为它们使 DNA 的两条链发生共价连接,ICLs 完全阻断转录和复制,因此对细胞是致命的。已经证实,参与 ICL 分解的蛋白质是核苷酸切除修复和同源重组功能的蛋白质。最近的工作,加上更早的一份报告,现在表明碱基切除修复途径的蛋白质与交联处理之间存在新的联系。