DNA ligase 4

Definition:

DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination. Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed. Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps. Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends. LIG4 regulates nuclear localization of XRCC4.

References:

[1]. P Robins, et al. DNA ligase IV from HeLa cell nuclei. J Biol Chem. 1996 Sep 27;271(39):24257-61. [Content Brief]

[2]. Dailia B Francis, et al. DNA Ligase IV regulates XRCC4 nuclear localization. DNA Repair (Amst). 2014 Sep;21:36-42. [Content Brief]

[3]. Jiafeng Gu, et al. XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps. EMBO J. 2007 Feb 21;26(4):1010-23. [Content Brief]

[4]. U Grawunder, et al. Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells. Nature. 1997 Jul 31;388(6641):492-5. [Content Brief]

[5]. L Chen, et al. Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase. J Biol Chem. 2000 Aug 25;275(34):26196-205. [Content Brief]

[6]. Jae Wan Lee, et al. Requirement for XRCC4 and DNA ligase IV in alignment-based gap filling for nonhomologous DNA end joining in vitro. Cancer Res. 2003 Jan 1;63(1):22-4. [Content Brief]

[7]. U Grawunder, et al. DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. Mol Cell. 1998 Oct;2(4):477-84. [Content Brief]

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