Interplay between DNA Polymerases and DNA Ligases: Influence on Substrate Channeling and the Fidelity of DNA Ligation. Issue 11 (17th May 2019)

• Record Type: Journal Article
• Authors: Çağlayan, Melike
• Is Part Of: Journal of molecular biology. Volume 431:Issue 11(2019)
• Page Start: 2068
• Page End: 2081
• Publication Date: 2019-05-17
• Subjects: genome stability -- DNA repair -- DNA polymerase -- DNA ligase -- ligation failure; OBD oligonucleotide binding domain -- AdD adenylation domain -- AMP adenosine monophosphate -- DBD DNA binding domain -- ATP adenosine triphosphate -- BER base excision repair -- dRP deoxyribose phosphate -- PCNA proliferating cell nuclear antigen -- DSB double-strand break -- ROS reactive oxygen species -- NHEJ nonhomologous end-joining -- MEF mouse embryonic fibroblast; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2019.04.028
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: DNA ligases are a highly conserved group of nucleic acid enzymes that play an essential role in DNA repair, replication, and recombination. This review focuses on functional interaction between DNA polymerases and DNA ligases in the repair of single- and double-strand DNA breaks, and discusses the notion that the substrate channeling during DNA polymerase-mediated nucleotide insertion coupled to DNA ligation could be a mechanism to minimize the release of potentially mutagenic repair intermediates. Evidence suggesting that DNA ligases are essential for cell viability includes the fact that defects or insufficiency in DNA ligase are casually linked to genome instability. In the future, it may be possible to develop small molecule inhibitors of mammalian DNA ligases and/or their functional protein partners that potentiate the effects of chemotherapeutic compounds and improve cancer treatment outcomes. Graphical abstract: Unlabelled Image Highlights: The substrate channeling from DNA polymerase β to DNA ligase during base excision repair pathway could prevent the accumulation of toxic repair intermediates. DNA ligases finalize the DNA repair, replication, and recombination and play critical role for maintaining genome stability. DNA ligase catalyzes a phosphodiester bond formation between adjacent 3′-OH and 5′-P termini of the nick DNA. The insertion of oxidized or mismatch nucleotide by a DNA polymerase could confound the next DNA ligation step during single-stranded and double-stranded DNA repair.