TY - JOUR
T1 - Substrate specificity of ultraviolet DNA endonuclease (UVDE/Uve1p) from Schizosaccharomyces pombe
AU - Avery, Angela M.
AU - Kaur, Balveen
AU - Taylor, John Stephen
AU - Mello, Jill A.
AU - Essigmann, John M.
AU - Doetsch, Paul W.
N1 - Funding Information:
We would like to thank Mu Wang and Yingie Ren of the Taylor laboratory for the preparation of the UV photoproduct-containing oligonucleotides. We would also like to thank members of the Doetsch laboratory for helpful discussions. This work was supported by Research Grants CA 73041 (P.W.D), CA 40463 (J.-S.T.) and CA 52127 (J.M.E.). A.M.A. was supported by an Elkin Fellowship from the Winship Cancer Center of Emory University.
PY - 1999/6/1
Y1 - 1999/6/1
N2 - Schizosaccharomyces pombe ultraviolet DNA endonuclease (UVDE or Uve1p) has been shown to cleave 5' to UV light-induced cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP). This endonuclease is believed to function in the initial step in an alternative excision repair pathway for the removal of DNA damage caused by exposure to UV light. An active truncated form of this protein, Δ228-Uve1p, has been successfully overexpressed, affinity purified and partially characterized. In the present study we present data from a detailed substrate specificity trial. We have determined that the substrate range of Uve1p is much greater than was originally believed. We demonstrate that this DNA damage repair protein is capable of recognizing an array of UV-induced DNA photoproducts (cis-syn-, trans-syn I- and trans-syn II CPDs, 6-4PP and Dewar isomers) that cause varying degrees of distortion in a duplex DNA molecule. We also demonstrate that Uve1p recognizes non-UV-induced DNA damage, such as platinum-DNA GG diadducts, uracil, dihydrouracil and abasic sites. This is the first time that a single DNA repair endonuclease with the ability to recognize such a diverse range of lesions has been described. This study suggests that Uve1p and the alternative excision repair pathway may participate broadly in the repair of DNA damage.
AB - Schizosaccharomyces pombe ultraviolet DNA endonuclease (UVDE or Uve1p) has been shown to cleave 5' to UV light-induced cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP). This endonuclease is believed to function in the initial step in an alternative excision repair pathway for the removal of DNA damage caused by exposure to UV light. An active truncated form of this protein, Δ228-Uve1p, has been successfully overexpressed, affinity purified and partially characterized. In the present study we present data from a detailed substrate specificity trial. We have determined that the substrate range of Uve1p is much greater than was originally believed. We demonstrate that this DNA damage repair protein is capable of recognizing an array of UV-induced DNA photoproducts (cis-syn-, trans-syn I- and trans-syn II CPDs, 6-4PP and Dewar isomers) that cause varying degrees of distortion in a duplex DNA molecule. We also demonstrate that Uve1p recognizes non-UV-induced DNA damage, such as platinum-DNA GG diadducts, uracil, dihydrouracil and abasic sites. This is the first time that a single DNA repair endonuclease with the ability to recognize such a diverse range of lesions has been described. This study suggests that Uve1p and the alternative excision repair pathway may participate broadly in the repair of DNA damage.
UR - http://www.scopus.com/inward/record.url?scp=0033151820&partnerID=8YFLogxK
U2 - 10.1093/nar/27.11.2256
DO - 10.1093/nar/27.11.2256
M3 - Article
C2 - 10325412
AN - SCOPUS:0033151820
SN - 0305-1048
VL - 27
SP - 2256
EP - 2264
JO - Nucleic acids research
JF - Nucleic acids research
IS - 11
ER -