DNA Ligase IV (LigIV) catalyzes nick sealing of DNA double-strand break substrates during non-homologous end-joining. Here the authors present the crystal structures of two human LigIV DNA-bound catalytic states, which provide insights into its catalytic mechanism and the molecular basis of LIG4 syndrome causing disease mutations.

DNA Ligase IV is a 911-aminoacid protein, a nuclear enzyme with a DNA binding domain and two BRCT motifs, involved in double strand DNA repair through the non-homologous end-joining (NHEJ) pathway, the major repair mechanism in mammalian cells, which consists of …

DNA ligase IV deficiency (OMIM 606593) or LIG4 syndrome (ORPHA99812), also known as Ligase 4 syndrome, is a rare autosomal recessive disorder characterised by microcephaly, abnormal facial features, sensitivity to ionizing radiation and combined immunodeficiency.

Two linked polymorphisms (A3V and T9I) were found to decrease the activity of DNA ligase IV by approximately 2-fold. When combined with the otherwise mild R278H mutation, ligase activity was reduced to a level similar to that of LIG4 patients with …

Nov 1, 2009 · A triple mutant (A3V + T9I + R278H) DNA ligase IV possesses a very low but still detectable residual activity in a nick ligation assay, which is less then 1% of the wild-type LIG4/XRCC4 activity.

Oct 15, 2014 · The DNA ligase IV is the crucial enzyme to for completing the non-homologous end joining (NHEJ) by forming a complex together with X-ray repair cross complementing protein 4 (XRCC4) for a final ligation of the break in an ATP-dependent step 6, 7.

Apr 2, 2013 · Here, we report the crystal structure at 2.4 Å resolution of the catalytic region of LigIV (residues 1–609) in complex with an Artemis peptide. We describe interactions of the DNA-binding domain of LigIV with the continuous epitope of …

Apr 4, 2012 · Two linked polymorphisms (A3V, 601837.0005; T9I, 601837.0006) were found to decrease the activity of DNA ligase IV by approximately 2-fold. When combined with the otherwise mild R278H (601837.0004) mutation, ligase activity was reduced to a level similar to that of LIG4 patients with immunodeficiency and developmental delay.

The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V (D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end …

DNA ligase IV deficiency is a rare autosomal recessive disorder associated with impaired DNA repair mechanisms. Most patients with DNA repair defects present with neurologic deficits, combined immunodeficiency, bone marrow failure, and/or hematologic neoplasia.