DNA ligases: Progress and prospects Journal Article
| Author: | Shuman, S. |
| Article Title: | DNA ligases: Progress and prospects |
| Abstract: | DNA ligases seal 5′-PO<sub>4</sub> and 3′-OH polynucleotide ends via three nucleotidyl transfer steps involving ligase-adenylate and DNA-adenylate intermediates. DNA ligases are essential guardians of genomic integrity, and ligase dysfunction underlies human genetic disease syndromes. Crystal structures of DNA ligases bound to nucleotide and nucleic acid substrates have illuminated how ligase reaction chemistry is catalyzed, how ligases recognize damaged DNA ends, and how protein domain movements and active-site remodeling are used to choreograph the end-joining pathway. Although a shared feature of DNA ligases is their envelopment of the nicked duplex as a C-shaped protein clamp, they accomplish this feat by using remarkably different accessory structural modules and domain topologies. As structural, biochemical, and phylogenetic insights coalesce, we can expect advances on several fronts, including (i) pharmacological targeting of ligases for antibacterial and anticancer therapies and (ii) the discovery and design of new strand-sealing enzymes with unique substrate specificities. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | nonhuman; drug targeting; antineoplastic agent; protein domain; dna damage; genes; high throughput screening; drug design; antiinfective agent; drug research; dna; nucleic acids; substrate specificity; short survey; crystal structure; dna structure; catalysis; structure analysis; polydeoxyribonucleotide synthase; enzyme specificity; drug determination; dna nucleotidylexotransferase; dna determination; enzymes; substrates; enzyme mechanism; nicotinamide adenine dinucleotide; dna ligases; enzyme active site; nucleotide; adenylate; anti-cancer therapies; c-shaped; domain topology; genomic integrity; human genetic disease; ligase reaction; ligases; polynucleotide; protein clamps; protein domains; structural module; nucleic acid; molecular phylogeny |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 284 |
| Issue: | 26 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2009-06-26 |
| Start Page: | 17365 |
| End Page: | 17369 |
| Language: | English |
| DOI: | 10.1074/jbc.R900017200 |
| PUBMED: | 19329793 |
| PROVIDER: | scopus |
| PMCID: | PMC2719376 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 30 November 2010" - "CODEN: JBCHA" - "Source: Scopus" |
