Crystal Structure of a Nucleotide Excision Repair Enzyme UvrB from Thermus thermophilus HB8

2000 ◽  
Vol 28 (5) ◽  
pp. A167-A167
Author(s):  
N. Nakagawa ◽  
M. Sugahara ◽  
R. Masui ◽  
R. Kato ◽  
K. Fukuyama ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Thermus Thermophilus ◽  
Repair Enzyme ◽  
Thermus Thermophilus Hb8 ◽  
Nucleotide Excision

scholarly journals Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines

Biochemistry ◽  
2010 ◽  
Vol 49 (6) ◽  
pp. 1053-1055 ◽  
Author(s):  
Pawel Jaruga ◽  
Yan Xiao ◽  
Vladimir Vartanian ◽  
R. Stephen Lloyd ◽  
Miral Dizdaroglu
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Repair Enzyme ◽  
Nucleotide Excision

scholarly journals Crystal Structure of the FeS Cluster–Containing Nucleotide Excision Repair Helicase XPD

PLoS Biology ◽  
2008 ◽  
Vol 6 (6) ◽  
pp. e149 ◽  
Author(s):  
Stefanie C Wolski ◽  
Jochen Kuper ◽  
Petra Hänzelmann ◽  
James J Truglio ◽  
Deborah L Croteau ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Nucleotide Excision

scholarly journals Impact of DNA sequences in the DNA duplex opening by the Rad4/XPC nucleotide excision repair complex

2020 ◽  
Author(s):  
Debamita Paul ◽  
Hong Mu ◽  
Qing Dai ◽  
Amirrasoul Tavakoli ◽  
Chuan He ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nucleotide Excision Repair ◽  
Dna Sequences ◽  
Excision Repair ◽  
Md Simulations ◽  
Dna Duplex ◽  
Open Structure ◽  
Dna Structures ◽  
Reverse Mode ◽  
Nucleotide Excision

ABSTRACTRad4/XPC is a key DNA damage sensor for nucleotide excision repair (NER) in eukaryotes. Rad4/XPC recognizes diverse bulky lesions by flipping out two lesion-containing nucleotide pairs and inserting a β-hairpin from the BHD3 domain (β-hairpin3) into the DNA duplex. We have previously observed that Rad4 can form the same ‘open’ structure when covalently tethered to a normal DNA sequence containing consecutive C/G’s (CCC/GGG) and that a similar open-like structure can be formed even when the β-hairpin3 is lacking. Here, we report a crystal structure of the Δβ-hairpin3 mutant tethered to a sequence containing alternating C/G’s (CGC/GCG). In contrast to the previous structures, Rad4 bound to CGC/GCG in a 180°-reversed manner, capping the end of the duplex without flipping out the nucleotides. MD simulations showed that CGC/GCG was inherently less ‘openable’ than CCC/GGG and that Rad4 failed to engage with its minor groove, a hallmark of productive binding towards ‘opening’. These results reveal that DNA sequences significantly influence the thermodynamic barrier for DNA opening by Rad4, which may render certain DNA structures/sequences resistant to ‘opening’ despite a long residence time of Rad4. The reverse- mode may indicate unproductive binding for NER whereas the DNA end-binding may hint at Rad4/XPC’s functions beyond NER.

scholarly journals Structure and mechanism of pyrimidine–pyrimidone (6-4) photoproduct recognition by the Rad4/XPC nucleotide excision repair complex

2019 ◽  
Vol 47 (12) ◽  
pp. 6015-6028 ◽  
Author(s):  
Debamita Paul ◽  
Hong Mu ◽  
Hong Zhao ◽  
Ouathek Ouerfelli ◽  
Philip D Jeffrey ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Md Simulations ◽  
Minor Groove ◽  
Pyrimidine Dimer ◽  
Structural Distortions ◽  
Nucleotide Excision ◽  
Radiation Induced ◽  
Uv Lesions

Abstract Failure in repairing ultraviolet radiation-induced DNA damage can lead to mutations and cancer. Among UV-lesions, the pyrimidine–pyrimidone (6-4) photoproduct (6-4PP) is removed from the genome much faster than the cyclobutane pyrimidine dimer (CPD), owing to the more efficient recognition of 6-4PP by XPC-RAD23B, a key initiator of global-genome nucleotide excision repair (NER). Here, we report a crystal structure of a Rad4–Rad23 (yeast XPC-Rad23B ortholog) bound to 6-4PP-containing DNA and 4-μs molecular dynamics (MD) simulations examining the initial binding of Rad4 to 6-4PP or CPD. This first structure of Rad4/XPC bound to a physiological substrate with matched DNA sequence shows that Rad4 flips out both 6-4PP-containing nucleotide pairs, forming an ‘open’ conformation. The MD trajectories detail how Rad4/XPC initiates ‘opening’ 6-4PP: Rad4 initially engages BHD2 to bend/untwist DNA from the minor groove, leading to unstacking and extrusion of the 6-4PP:AA nucleotide pairs towards the major groove. The 5′ partner adenine first flips out and is captured by a BHD2/3 groove, while the 3′ adenine extrudes episodically, facilitating ensuing insertion of the BHD3 β-hairpin to open DNA as in the crystal structure. However, CPD resists such Rad4-induced structural distortions. Untwisting/bending from the minor groove may be a common way to interrogate DNA in NER.

Sign in / Sign up

Export Citation Format

Share Document