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Biochemistry. 2009 Aug 18;48(32):7565-7. doi: 10.1021/bi901006b.

Double-strand break formation during nucleotide excision repair of a DNA interstrand cross-link.

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  • 1Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, USA.


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.

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