DNA quality control by conformational readout on the undamaged strand of the double helix.
Synthetic DNA probes were incubated in human cell extracts to dissect the early step of bulky lesion recognition in the nucleotide excision repair pathway. Excision was induced upon combination of the target adduct with either a two-sided bulge, involving both the damaged sequence and its undamaged partner strand, or a one-sided bulge, affecting exclusively the undamaged complementary sequence. Surprisingly, the same adduct became refractory to repair when only the modified strand was bulged out of the double helix. Adduct removal was further dependent on an intact opposing strand and, at carcinogen-DNA adducts, the assembly of excision complexes was triggered by a single flipped-out deoxyribonucleotide in the complementary sequence. These findings describe a mechanism of molecular readout in DNA repair that, unexpectedly, is entirely confined to the undamaged side of the double helix.
Buterin
Tonko
T
Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, 8057 Zürich, Switzerland.
Meyer
Christoph
C
Giese
Bernd
B
Naegeli
Hanspeter
H
D000595:Amino Acid Sequence; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism; D015342:DNA Probes / Q000737:chemistry; D004260:DNA Repair; D018076:DNA, Complementary / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism / Q000502:physiology; D009690:Nucleic Acid Conformation
D018736:DNA Adducts; D015342:DNA Probes; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C086984:XPC protein, human; D004247:DNA