Double-strand break formation during nucleotide excision repair of a DNA interstrand cross-link.
The DNA interstrand cross-link (ICL) resulting from the C4'-oxidized abasic site (C4-AP) is a unique clustered lesion comprised of a cross-link adjacent to a nick. The ICL is a substrate for the UvrABC nucleotide excision repair system. The strand containing the nick is preferentially incised, but the nick influences the cleavage sites. Moreover, in approximately 15% of the molecules, the strand opposite the nick is incised, resulting in a more toxic double-strand break. This is the first example in which an interstrand cross-link is converted by nucleotide excision misrepair into a more deleterious double-strand break.
Sczepanski
Jonathan T
JT
Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Jacobs
Aaron C
AC
Van Houten
Bennett
B
Greenberg
Marc M
MM
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure
D029968:Escherichia coli Proteins; D004247:DNA; D004706:Endodeoxyribonucleases; C036385:endodeoxyribonuclease uvrABC