NEIL3糖基化酶对DNA链间交联进行依赖复制的解钩作用。
Replication-Dependent Unhooking of DNA Interstrand Cross-Links by the NEIL3 Glycosylase.
作者信息
Semlow Daniel R, Zhang Jieqiong, Budzowska Magda, Drohat Alexander C, Walter Johannes C
机构信息
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
出版信息
Cell. 2016 Oct 6;167(2):498-511.e14. doi: 10.1016/j.cell.2016.09.008. Epub 2016 Sep 29.
During eukaryotic DNA interstrand cross-link (ICL) repair, cross-links are resolved ("unhooked") by nucleolytic incisions surrounding the lesion. In vertebrates, ICL repair is triggered when replication forks collide with the lesion, leading to FANCI-FANCD2-dependent unhooking and formation of a double-strand break (DSB) intermediate. Using Xenopus egg extracts, we describe here a replication-coupled ICL repair pathway that does not require incisions or FANCI-FANCD2. Instead, the ICL is unhooked when one of the two N-glycosyl bonds forming the cross-link is cleaved by the DNA glycosylase NEIL3. Cleavage by NEIL3 is the primary unhooking mechanism for psoralen and abasic site ICLs. When N-glycosyl bond cleavage is prevented, unhooking occurs via FANCI-FANCD2-dependent incisions. In summary, we identify an incision-independent unhooking mechanism that avoids DSB formation and represents the preferred pathway of ICL repair in a vertebrate cell-free system.
在真核生物DNA链间交联（ICL）修复过程中，交联通过损伤周围的核酸酶切割得以解决（“解开”）。在脊椎动物中，当复制叉与损伤部位碰撞时，ICL修复被触发，导致FANCI-FANCD2依赖的解开以及双链断裂（DSB）中间体的形成。利用非洲爪蟾卵提取物，我们在此描述了一种复制偶联的ICL修复途径，该途径不需要切割或FANCI-FANCD2。相反，当形成交联的两个N-糖苷键之一被DNA糖基化酶NEIL3切割时，ICL被解开。NEIL3的切割是补骨脂素和无碱基位点ICL的主要解钩机制。当N-糖苷键切割被阻止时，解钩通过FANCI-FANCD2依赖的切割发生。总之，我们鉴定出一种不依赖切割的解钩机制，该机制可避免DSB形成，并且是脊椎动物无细胞系统中ICL修复的首选途径。
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