Crystal structure of the DNA repair enzyme ultraviolet damage endonuclease.
The ultraviolet damage endonuclease (UVDE) performs the initial step in an alternative excision repair pathway of UV-induced DNA damage, nicking immediately adjacent to the 5' phosphate of the damaged nucleotides. Unique for a single-protein DNA repair endonuclease, it can detect different types of damage. Here we show that Thermus thermophilus UVDE shares some essential structural features with Endo IV, an enzyme from the base excision repair pathway that exclusively nicks at abasic sites. A comparison between the structures indicates how DNA is bound by UVDE, how UVDE may recognize damage, and which of its residues are involved in catalysis. Furthermore, the comparison suggests an elegant explanation of UVDE's potential to recognize different types of damage. Incision assays including point mutants of UVDE confirmed the relevance of these conclusions.
Paspaleva
Keti
K
Laboratory of Molecular Genetics, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Thomassen
Ellen
E
Pannu
Navraj S
NS
Iwai
Shigenori
S
Moolenaar
Geri F
GF
Goosen
Nora
N
Abrahams
Jan Pieter
JP
D020137:Base Pair Mismatch; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000737:chemistry* / Q000378:metabolism; D043223:Deoxyribonuclease IV (Phage T4-Induced) / Q000737:chemistry / Q000378:metabolism; D004720:Endonucleases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D016415:Sequence Alignment; D016963:Thermus thermophilus / Q000201:enzymology; D014466:Ultraviolet Rays
D004247:DNA; D004720:Endonucleases; D043223:Deoxyribonuclease IV (Phage T4-Induced); D045643:DNA Repair Enzymes