Inhibition of Replication Fork Formation and Progression: Targeting the Replication Initiation and Primosomal Proteins

Radford, Holly M., Toft, Casey J., Sorenson, Alanna E., and Schaeffer, Patrick M. (2023) Inhibition of Replication Fork Formation and Progression: Targeting the Replication Initiation and Primosomal Proteins. International Journal of Molecular Sciences, 24 (10). 8802.

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DOI: 10.3390/ijms24108802

View at Publisher Website: https://doi.org/10.3390/ijms24108802

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Abstract

Over 1.2 million deaths are attributed to multi-drug-resistant (MDR) bacteria each year. Persistence of MDR bacteria is primarily due to the molecular mechanisms that permit fast replication and rapid evolution. As many pathogens continue to build resistance genes, current antibiotic treatments are being rendered useless and the pool of reliable treatments for many MDR-associated diseases is thus shrinking at an alarming rate. In the development of novel antibiotics, DNA replication is still a largely underexplored target. This review summarises critical literature and synthesises our current understanding of DNA replication initiation in bacteria with a particular focus on the utility and applicability of essential initiation proteins as emerging drug targets. A critical evaluation of the specific methods available to examine and screen the most promising replication initiation proteins is provided.


Item ID:	79943
Item Type:	Article (Research - C1)
ISSN:	1422-0067
Keywords:	DNA replication, antibiotics, primase, helicase, high-throughput screening, replication fork, replisome, DnaA, bacteria
Copyright Information:	© 2023 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Date Deposited:	18 Aug 2023 07:07
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 30% 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310106 Enzymes @ 20% 34 CHEMICAL SCIENCES > 3404 Medicinal and biomolecular chemistry > 340499 Medicinal and biomolecular chemistry not elsewhere classified @ 50%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 50% 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 50%
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