Bleomycin mediated degradation of DNA-RNA hybrids does not involve C-1' chemistry.
Incubation of Fe(II) bleomycin and O2 with a number of 'A'-like DNA-RNA hybrid homopolymers at 4 atm O2 results in formation of base propenal and base in a ratio of approximately 1.0:1.0. This ratio differs dramatically from the corresponding ratio of approximately 10:1.0 observed when activated BLM degrades 'B'-like DNA homopolymers. Experiments were undertaken to determine if the shift to enhanced base production observed in the A-like hybrids is the result of C-1' chemistry in addition to the C-4' chemistry normally observed with B-like DNA under identical conditions. Increased accessibility of the 1'-hydrogen might be anticipated due to widening of the minor groove in the A-like conformers. Experiments using poly([1'-3H]dA) poly(rU) and poly([U-14C]dA) poly(rU) indicated that neither 3H2O nor deoxyribonolactone accompanied adenine release. In addition, studies using poly([4'-2H]dA) poly(rU) and poly([1'-2H]dA) poly(rU) unambiguously establish that the altered base to base propenal ratio is not the result of C-1' chemistry, but a direct consequence of C-4' chemistry.
Absalon
M J
MJ
Department of Chemistry and Biology, Massachusetts Institute of Technology, Cambridge 02139.
Krishnamoorthy
C R
CR
McGall
G
G
Kozarich
J W
JW
Stubbe
J
J
D001761:Bleomycin / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D011089:Polydeoxyribonucleotides / Q000737:chemistry*; D011131:Polyribonucleotides / Q000737:chemistry*
D011089:Polydeoxyribonucleotides; D011131:Polyribonucleotides; D001761:Bleomycin; D010100:Oxygen