DNA adduct structure-function relationships: comparing solution with polymerase structures.
It has now been nearly two decades since the first solution structures of DNA duplexes covalently damaged by metabolically activated polycyclic aromatic hydrocarbons and amines were determined by NMR. Dozens of such high-resolution structures are now available, and some broad structural themes have been uncovered. It has been hypothesized that the solution structures are relevant to the biochemical processing of the adducts. The structural features of the adducts are considered to determine their mutational properties in DNA polymerases and their repair susceptibilities. In recent years, a number of crystal structures of DNA adducts of interest to our work have been determined in DNA polymerases. Accordingly, it is now timely to consider how NMR solution structures relate to structures within DNA polymerases. The NMR solution structural themes for polycyclic aromatic adducts are often observed in polymerase crystal structures. While the polymerase interactions can on occasion override the solution preferences, intrinsic adduct conformations favored in solution are often manifested within polymerases and likely play a significant role in lesion processing.
Broyde
Suse
S
Department of Biology, New York University, New York NY 10003, USA. broyde@nyu.edu
Wang
Lihua
L
Zhang
Ling
L
Rechkoblit
Olga
O
Geacintov
Nicholas E
NE
Patel
Dinshaw J
DJ
D000818:Animals; D018736:DNA Adducts / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009154:Mutation / Q000235:genetics; D009690:Nucleic Acid Conformation; D012996:Solutions; D013329:Structure-Activity Relationship
D018736:DNA Adducts; D012996:Solutions; D004259:DNA-Directed DNA Polymerase