title: The DNA ligase III zinc finger stimulates binding to DNA secondary structure and promotes end joining.
abstract: The ability to rejoin broken chromosomes is fundamental to the maintenance of genetic integrity. Mammalian cells possess at least five DNA ligases, including three isoforms of DNA ligase III (Lig-3). Lig-3 proteins differ from other DNA ligases in the presence of an N-terminal zinc finger (Zn-f) motif that exhibits extensive homology with two zinc fingers in poly(ADP-ribose) polymerase (PARP). Here we report that the Zn-f confers upon Lig-3 the ability to bind DNA duplexes harbouring a variety of DNA secondary structures, including single-strand gaps and single-strand flaps. Moreover, the Zn-f stimulates intermolecular end joining of duplexes that harbour these structures up to 16-fold. The Zn-f also stimulates end joining between duplexes lacking secondary structure, but to a lesser extent (up to 4-fold). We conclude that the Zn-f may enable Lig-3 to rejoin chromosomal DNA strand breaks located at sites of clustered damage induced by ionising radiation or near to secondary structure intermediates of DNA metabolism.
authors.affiliation: School of Biological Sciences, G.38 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Taylor
authors.forename: C J
authors.initials: CJ
authors.lastname: Whitehouse
authors.forename: K W
authors.initials: KW
authors.lastname: Caldecott
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D009690:Nucleic Acid Conformation; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins; D016335:Zinc Fingers
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D011994:Recombinant Proteins; D029867:Xenopus Proteins; D004247:DNA; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human