Structural highlights
Function
[RAD4_YEAST] Involved in nucleotide excision repair of DNA damaged with UV light, bulky adducts, or cross-linking agents. [RAD23_YEAST] Plays a central role both in proteasomal degradation of misfolded proteins and DNA repair. Central component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. Involved in DNA excision repair. May play a part in DNA damage recognition and/or in altering chromatin structure to allow access by damage-processing enzymes.
Publication Abstract from PubMed
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.
Kinetic gating mechanism of DNA damage recognition by Rad4/XPC.,Chen X, Velmurugu Y, Zheng G, Park B, Shim Y, Kim Y, Liu L, Van Houten B, He C, Ansari A, Min JH Nat Commun. 2015 Jan 6;6:5849. doi: 10.1038/ncomms6849. PMID:25562780[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen X, Velmurugu Y, Zheng G, Park B, Shim Y, Kim Y, Liu L, Van Houten B, He C, Ansari A, Min JH. Kinetic gating mechanism of DNA damage recognition by Rad4/XPC. Nat Commun. 2015 Jan 6;6:5849. doi: 10.1038/ncomms6849. PMID:25562780 doi:http://dx.doi.org/10.1038/ncomms6849
