title: Single-stranded DNA ligation and XLF-stimulated incompatible DNA end ligation by the XRCC4-DNA ligase IV complex: influence of terminal DNA sequence.
abstract: The double-strand DNA break repair pathway, non-homologous DNA end joining (NHEJ), is distinctive for the flexibility of its nuclease, polymerase and ligase activities. Here we find that the joining of ends by XRCC4-ligase IV is markedly influenced by the terminal sequence, and a steric hindrance model can account for this. XLF (Cernunnos) stimulates the joining of both incompatible DNA ends and compatible DNA ends at physiologic concentrations of Mg2+, but only of incompatible DNA ends at higher concentrations of Mg2+, suggesting charge neutralization between the two DNA ends within the ligase complex. XRCC4-DNA ligase IV has the distinctive ability to ligate poly-dT single-stranded DNA and long dT overhangs in a Ku- and XLF-independent manner, but not other homopolymeric DNA. The dT preference of the ligase is interesting given the sequence bias of the NHEJ polymerase. These distinctive properties of the XRCC4-DNA ligase IV complex explain important aspects of its in vivo roles.
authors: Department of Pathology, Biochemistry & Molecular Biology, Biological Sciences, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors: Jiafeng
authors: J
authors: Gu
authors: Haihui
authors: H
authors: Lu
authors: Albert G
authors: AG
authors: Tsai
authors: Klaus
authors: K
authors: Schwarz
authors: Michael R
authors: MR
authors: Lieber
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000737:chemistry
chemical_list: D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C000607893:LIG4 protein, human; C508551:NHEJ1 protein, human; C101467:XRCC4 protein, human; D004247:DNA; D011088:DNA Ligases; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP; D008274:Magnesium
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