Truglio James J, Karakas Erkan, Rhau Benjamin, Wang Hong, DellaVecchia Matthew J, Van Houten Bennett, Kisker Caroline
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794-5115, USA.
Nat Struct Mol Biol. 2006 Apr;13(4):360-4. doi: 10.1038/nsmb1072. Epub 2006 Mar 12.
DNA-damage recognition in the nucleotide excision repair (NER) cascade is a complex process, operating on a wide variety of damages. UvrB is the central component in prokaryotic NER, directly involved in DNA-damage recognition and guiding the DNA through repair synthesis. We report the first structure of a UvrB-double-stranded DNA complex, providing insights into the mechanism by which UvrB binds DNA, leading to formation of the preincision complex. One DNA strand, containing a 3' overhang, threads behind a beta-hairpin motif of UvrB, indicating that this motif inserts between the strands of the double helix, thereby locking down either the damaged or undamaged strand. The nucleotide directly behind the beta-hairpin is flipped out and inserted into a small, highly conserved pocket in UvrB.
核苷酸切除修复(NER)级联反应中的DNA损伤识别是一个复杂的过程,作用于多种损伤。UvrB是原核生物NER的核心成分,直接参与DNA损伤识别并引导DNA进行修复合成。我们报道了UvrB与双链DNA复合物的首个结构,为UvrB结合DNA从而导致切口前复合物形成的机制提供了见解。一条含有3'端突出端的DNA链穿入UvrB的一个β-发夹基序后方,这表明该基序插入双螺旋的两条链之间,从而锁定受损或未受损的链。β-发夹后方的核苷酸被翻转出来并插入UvrB中一个小的、高度保守的口袋中。