Sarangi Prabha, Altmannova Veronika, Holland Cory, Bartosova Zdenka, Hao Fanfan, Anrather Dorothea, Ammerer Gustav, Lee Sang Eun, Krejci Lumir, Zhao Xiaolan
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
Department of Biology, Masaryk University, Brno 62500, Czech Republic.
Cell Rep. 2014 Oct 9;9(1):143-152. doi: 10.1016/j.celrep.2014.08.054. Epub 2014 Sep 25.
DNA repair scaffolds mediate specific DNA and protein interactions in order to assist repair enzymes in recognizing and removing damaged sequences. Many scaffold proteins are dedicated to repairing a particular type of lesion. Here, we show that the budding yeast Saw1 scaffold is more versatile. It helps cells cope with base lesions and protein-DNA adducts through its known function of recruiting the Rad1-Rad10 nuclease to DNA. In addition, it promotes UV survival via a mechanism mediated by its sumoylation. Saw1 sumoylation favors its interaction with another nuclease Slx1-Slx4, and this SUMO-mediated role is genetically separable from two main UV lesion repair processes. These effects of Saw1 and its sumoylation suggest that Saw1 is a multifunctional scaffold that can facilitate diverse types of DNA repair through its modification and nuclease interactions.
DNA修复支架介导特定的DNA与蛋白质相互作用,以协助修复酶识别和去除受损序列。许多支架蛋白专门用于修复特定类型的损伤。在此,我们表明芽殖酵母Saw1支架具有更多功能。它通过将Rad1-Rad10核酸酶招募到DNA的已知功能,帮助细胞应对碱基损伤和蛋白质-DNA加合物。此外,它通过一种由其SUMO化介导的机制促进紫外线照射后的存活。Saw1的SUMO化有利于其与另一种核酸酶Slx1-Slx4的相互作用,并且这种SUMO介导的作用在遗传上与两个主要的紫外线损伤修复过程是可分离的。Saw1及其SUMO化的这些作用表明,Saw1是一种多功能支架,可通过其修饰和核酸酶相互作用促进多种类型的DNA修复。