What does LIG4 do in response to DNA breaks?
LIG4 is an ATP-dependent DNA ligase. LIG4 uses ATP to adenylate itself and then transfers the AMP group to the 5′ phosphate of one DNA end. Nucleophilic attack by the 3′ hydroxyl group of a second DNA end and release of AMP yield the ligation product. Adenylation of LIG4 is stimulated by XRCC4 and XLF.
What does a DNA ligase do?
DNA ligases catalyze the formation of a phosphodiester bond between DNA single strands in the duplex form (Fig. 2.1). The covalent linkage of the 5′-P group of one chain with the adjacent 3′-OH group of another is coupled with the pyrophosphate hydrolysis of the cofactor ATP or NAD.
Does ligase repair DNA?
DNA ligase is a specific type of enzyme, a ligase, (EC 6.5. 1.1) that facilitates the joining of DNA strands together by catalyzing the formation of a phosphodiester bond. DNA ligase is used in both DNA repair and DNA replication (see Mammalian ligases).
How is a ligase molecule used in DNA synthesis?
On the lagging strand, DNA synthesis restarts many times as the helix unwinds, resulting in many short fragments called “Okazaki fragments.” DNA ligase joins the Okazaki fragments together into a single DNA molecule.
How does T4 ligase work?
T4 DNA Ligase catalyzes the joining of two cohesive- or blunt-ended strands of DNA between the 5´-phosphate and the 3´-hydroxyl groups of adjacent nucleotides. The enzyme will not join single-stranded nucleic acids.
What is the substrate for ligases?
Ligases catalyze the formation of phosphodiester bond between 3′OH and 5′phosphate on various substrates such as DNA nicks, DNA fragments with various lengths cohesive ends, DNA fragments with blunt ends and some DNA/RNA hybrids.
What is the pathophysiology of LIG4 syndrome?
LIG4 syndrome is characterized by pancytopaenia, developmental and growth delay. Hypomorphic mutations in DNA ligase IV have been found in LIG4 syndrome patients, all of which markedly impact upon the protein function. One of the five patients identified developed leukaemia and showed dramatic clinical radiosensitivity.
What is the mechanism of adenylation of LIG4?
LIG4 is an ATP-dependent DNA ligase. LIG4 uses ATP to adenylate itself and then transfers the AMP group to the 5′ phosphate of one DNA end. Nucleophilic attack by the 3′ hydroxyl group of a second DNA end and release of AMP yield the ligation product. Adenylation of LIG4 is stimulated by XRCC4 and XLF.
What does LIG4 stand for?
DNA ligase 4 is an enzyme that in humans is encoded by the LIG4 gene. The protein encoded by this gene is an ATP -dependent DNA ligase that joins double-strand breaks during the non-homologous end joining pathway of double-strand break repair.
What is dnadna ligase 4 (Lig4)?
DNA ligase 4 is an enzyme that in humans is encoded by the LIG4 gene.