SNAP output for PDB entry 4yir [SNAP web server]

PDB-id

4yir; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-DNA

Method

X-ray (3.05 Å)

Summary

Crystal structure of rad4-rad23 crosslinked to an undamaged DNA

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.