SNAP output for PDB entry 6ubf [SNAP web server]

PDB-id

6ubf; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-DNA

Method

X-ray (4.597 Å)

Summary

Role of beta-hairpin motifs in the DNA duplex opening by the rad4-xpc nucleotide excision repair complex

Reference

Chen X, Velmurugu Y, Zheng G, Park B, Shim Y, Kim Y, Liu L, Van Houten B, He C, Ansari A, Min JH (2015): "Kinetic gating mechanism of DNA damage recognition by Rad4/XPC." Nat Commun, 6, 5849. doi: 10.1038/ncomms6849.

Abstract

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.