Mammalian DNA ligases; roles in maintaining genome integrity.

Autor: Sallmyr A; University of New Mexico Comprehensive Cancer Center and the Departments of Internal Medicine, and Molecular Genetics & Microbiology, University of New Mexico Health Sciences Center, United States., Bhandari SK; University of New Mexico Comprehensive Cancer Center and the Departments of Internal Medicine, and Molecular Genetics & Microbiology, University of New Mexico Health Sciences Center, United States., Naila T; University of New Mexico Comprehensive Cancer Center and the Departments of Internal Medicine, and Molecular Genetics & Microbiology, University of New Mexico Health Sciences Center, United States., Tomkinson AE; University of New Mexico Comprehensive Cancer Center and the Departments of Internal Medicine, and Molecular Genetics & Microbiology, University of New Mexico Health Sciences Center, United States. Electronic address: atomkinson@salud.unm.edu.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2024 Jan 01; Vol. 436 (1), pp. 168276. Date of Electronic Publication: 2023 Sep 13.
DOI: 10.1016/j.jmb.2023.168276
Abstrakt: The joining of breaks in the DNA phosphodiester backbone is essential for genome integrity. Breaks are generated during normal processes such as DNA replication, cytosine demethylation during differentiation, gene rearrangement in the immune system and germ cell development. In addition, they are generated either directly by a DNA damaging agent or indirectly due to damage excision during repair. Breaks are joined by a DNA ligase that catalyzes phosphodiester bond formation at DNA nicks with 3' hydroxyl and 5' phosphate termini. Three human genes encode ATP-dependent DNA ligases. These enzymes have a conserved catalytic core consisting of three subdomains that encircle nicked duplex DNA during ligation. The DNA ligases are targeted to different nuclear DNA transactions by specific protein-protein interactions. Both DNA ligase IIIα and DNA ligase IV form stable complexes with DNA repair proteins, XRCC1 and XRCC4, respectively. There is functional redundancy between DNA ligase I and DNA ligase IIIα in DNA replication, excision repair and single-strand break repair. Although DNA ligase IV is a core component of the major double-strand break repair pathway, non-homologous end joining, the other enzymes participate in minor, alternative double-strand break repair pathways. In contrast to the nucleus, only DNA ligase IIIα is present in mitochondria and is essential for maintaining the mitochondrial genome. Human immunodeficiency syndromes caused by mutations in either LIG1 or LIG4 have been described. Preclinical studies with DNA ligase inhibitors have identified potentially targetable abnormalities in cancer cells and evidence that DNA ligases are potential targets for cancer therapy.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: