title: Nick-dependent and -independent processing of large DNA loops in human cells.
abstract: DNA loop heterologies are products of normal DNA metabolism and can lead to severe genomic instability if unrepaired. To understand how human cells process DNA loop structures, a set of circular heteroduplexes containing a 30-nucleotide loop were constructed and tested for repair in vitro by human cell nuclear extracts. We demonstrate here that, in addition to the previously identified 5' nick-directed loop repair pathway (Littman, S. J., Fang, W. H., and Modrich, P. (1999) J. Biol. Chem. 274, 7474-7481), human cells can process large DNA loop heterologies in a loop-directed manner. The loop-directed repair specifically removes the loop structure and occurs only in the looped strand, and appears to require limited DNA synthesis. Like the nick-directed loop repair, the loop-directed repair is independent of many known DNA repair pathways, including DNA mismatch repair and nucleotide excision repair. In addition, our data also suggest that an aphidicolin-sensitive DNA polymerase is involved in the excision step of the nick-directed loop repair pathway.
authors.affiliation: Graduate Center for Toxicology, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: McCulloch
authors.forename: Liya
authors.initials: L
authors.lastname: Gu
authors.forename: Guo-Min
authors.initials: GM
authors.lastname: Li
mesh_terms: D016590:Aphidicolin / Q000494:pharmacology; D001435:Bacteriophages / Q000378:metabolism; D020137:Base Pair Mismatch; D020029:Base Pairing; D001483:Base Sequence; D015139:Blotting, Southern; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes
chemical_list: D004791:Enzyme Inhibitors; D009692:Nucleic Acid Heteroduplexes; D016590:Aphidicolin; D004247:DNA; D004259:DNA-Directed DNA Polymerase