Pokorny Richard, Klar Tobias, Hennecke Ulrich, Carell Thomas, Batschauer Alfred, Essen Lars-Oliver
Department of Biology, Philipps University, Karl-von-Frisch-Strasse 8, D-35032 Marburg, Germany.
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):21023-7. doi: 10.1073/pnas.0805830106. Epub 2008 Dec 12.
DNA photolyases and cryptochromes (cry) form a family of flavoproteins that use light energy in the blue/UV-A region for the repair of UV-induced DNA lesions or for signaling, respectively. Very recently, it was shown that members of the DASH cryptochrome subclade repair specifically cyclobutane pyrimidine dimers (CPDs) in UV-damaged single-stranded DNA. Here, we report the crystal structure of Arabidopsis cryptochrome 3 with an in-situ-repaired CPD substrate in single-stranded DNA. The structure shows a binding mode similar to that of conventional DNA photolyases. Furthermore, CPD lesions in double-stranded DNA are bound and repaired with similar efficiency as in single-stranded DNA if the CPD lesion is present in a loop structure. Together, these data reveal that DASH cryptochromes catalyze light-driven DNA repair like conventional photolyases but lack an efficient flipping mechanism for interaction with CPD lesions within duplex DNA.
DNA光解酶和隐花色素（cry）构成了一类黄素蛋白家族，它们分别利用蓝光/UV-A区域的光能来修复紫外线诱导的DNA损伤或进行信号传导。最近，研究表明DASH隐花色素亚分支的成员专门修复紫外线损伤的单链DNA中的环丁烷嘧啶二聚体（CPD）。在此，我们报道了拟南芥隐花色素3与单链DNA中经原位修复的CPD底物的晶体结构。该结构显示出与传统DNA光解酶相似的结合模式。此外，如果CPD损伤存在于环结构中，双链DNA中的CPD损伤与单链DNA中的CPD损伤以相似的效率被结合和修复。总之，这些数据表明DASH隐花色素像传统光解酶一样催化光驱动的DNA修复，但缺乏与双链DNA内CPD损伤相互作用的有效翻转机制。
