The Fanconi anemia (FA) pathway repairs DNA interstrand crosslinks (ICLs). Many FA proteins are recruited to ICLs in a timely fashion so that coordinated repair can occur. However, the mechanism of this process is poorly understood. Here, we report the purification of a FANCD2-containing protein complex with multiple subunits, including WRNIP1. Using live-cell imaging, we show that WRNIP1 is recruited to ICLs quickly after their appearance, promoting repair. The observed recruitment facilitates subsequent recruitment of the FANCD2/FANCI complex. Depletion of WRNIP1 sensitizes cells to ICL-forming drugs. We find that ubiquitination of WRNIP1 and the activity of its UBZ domain are required to facilitate recruitment of FANCD2/FANCI and promote repair. Altogether, we describe a mechanism by which WRNIP1 is recruited rapidly to ICLs, resulting in chromatin loading of the FANCD2/FANCI complex in an unusual process entailing ubiquitination of WRNIP1 and the activity of its integral UBZ domain.

范可尼贫血（FA）途径可修复DNA链间交联（ICL）。及时将许多FA蛋白募集到ICL中，以便进行协调的修复。但是，对该过程的机制了解甚少。在这里，我们报告包含多个WWIP1多个亚基的含FANCD2的蛋白质复合物的纯化。使用活细胞成像，我们显示WRNIP1在出现后迅速被募集到ICL，从而促进修复。观察到的募集有助于随后募集FANCD2 / FANCI复合体。WRNIP1的耗尽会使细胞对ICL形成药物敏感。我们发现WRNIP1的泛素化及其UBZ域的活性是促进FANCD2 / FANCI募集和促进修复所必需的。总而言之，我们描述了一种将WRNIP1快速招募到ICL的机制，