Mechanistic coupling of enzymatic activities at the replisome.
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| Title: | Mechanistic coupling of enzymatic activities at the replisome. |
|---|---|
| Authors: | Welikala, Malisha U.1 michael_trakselis@baylor.edu, Butterworth, Lauren J.1, Beragama Arachchi, Rashini Y.1, Trakselis, Michael A.1 |
| Source: | Journal of Biological Chemistry. Nov2025, Vol. 301 Issue 11, p1-20. 20p. |
| Subjects: | DNA replication, Replisomes, Enzymology, Helicases, DNA polymerases, Polymerases, DNA repair |
| Abstract: | DNA replication is a vital process requiring the synergistic coordination of enzymatic activities that include unwinding, priming, and synthesis. The helicase serves as the central hub of the replisome and maintains interactions with the enzymes involved in priming and synthesis, which can alter respective structural conformations to control kinetics. This review compares how evolutionarily diverse model systems from phage, Escherichia coli, and eukaryotes mechanistically couple these functions to maintain replication stability amid genomic challenges. Despite vast differences in complexity, all systems exhibit conserved principles of coordination through helicase– primase and helicase–polymerase interactions, facilitated by direct binding, intermediary proteins, or conformational constraints. We explore the structural and functional dynamics of replisome architecture, highlighting how core enzymes and accessory proteins collaborate to stabilize and regulate these complexes. Differences in replisome complexity, from the streamlined T7 to more intricate eukaryotic systems, underscore conserved and adaptive strategies for replication regulation. Consequences of replisome blocks leading to stalled forks or decoupled unwinding and synthesis, giving rise to singlestrand gaps, are discussed in the context of conserved regulatory responses. Together, we provide insight into universal and divergent replisomal coupling mechanisms, offering a foundation for understanding replication-associated diseases and informing on novel therapeutic approaches. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 189659571 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Mechanistic coupling of enzymatic activities at the replisome. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Welikala%2C+Malisha+U%2E%22">Welikala, Malisha U.</searchLink><relatesTo>1</relatesTo><i> michael_trakselis@baylor.edu</i><br /><searchLink fieldCode="AR" term="%22Butterworth%2C+Lauren+J%2E%22">Butterworth, Lauren J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Beragama+Arachchi%2C+Rashini+Y%2E%22">Beragama Arachchi, Rashini Y.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Trakselis%2C+Michael+A%2E%22">Trakselis, Michael A.</searchLink><relatesTo>1</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. Nov2025, Vol. 301 Issue 11, p1-20. 20p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22DNA+replication%22">DNA replication</searchLink><br /><searchLink fieldCode="DE" term="%22Replisomes%22">Replisomes</searchLink><br /><searchLink fieldCode="DE" term="%22Enzymology%22">Enzymology</searchLink><br /><searchLink fieldCode="DE" term="%22Helicases%22">Helicases</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+polymerases%22">DNA polymerases</searchLink><br /><searchLink fieldCode="DE" term="%22Polymerases%22">Polymerases</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+repair%22">DNA repair</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: DNA replication is a vital process requiring the synergistic coordination of enzymatic activities that include unwinding, priming, and synthesis. The helicase serves as the central hub of the replisome and maintains interactions with the enzymes involved in priming and synthesis, which can alter respective structural conformations to control kinetics. This review compares how evolutionarily diverse model systems from phage, Escherichia coli, and eukaryotes mechanistically couple these functions to maintain replication stability amid genomic challenges. Despite vast differences in complexity, all systems exhibit conserved principles of coordination through helicase– primase and helicase–polymerase interactions, facilitated by direct binding, intermediary proteins, or conformational constraints. We explore the structural and functional dynamics of replisome architecture, highlighting how core enzymes and accessory proteins collaborate to stabilize and regulate these complexes. Differences in replisome complexity, from the streamlined T7 to more intricate eukaryotic systems, underscore conserved and adaptive strategies for replication regulation. Consequences of replisome blocks leading to stalled forks or decoupled unwinding and synthesis, giving rise to singlestrand gaps, are discussed in the context of conserved regulatory responses. Together, we provide insight into universal and divergent replisomal coupling mechanisms, offering a foundation for understanding replication-associated diseases and informing on novel therapeutic approaches. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=189659571 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.jbc.2025.110761 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 20 StartPage: 1 Subjects: – SubjectFull: DNA replication Type: general – SubjectFull: Replisomes Type: general – SubjectFull: Enzymology Type: general – SubjectFull: Helicases Type: general – SubjectFull: DNA polymerases Type: general – SubjectFull: Polymerases Type: general – SubjectFull: DNA repair Type: general Titles: – TitleFull: Mechanistic coupling of enzymatic activities at the replisome. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Welikala, Malisha U. – PersonEntity: Name: NameFull: Butterworth, Lauren J. – PersonEntity: Name: NameFull: Beragama Arachchi, Rashini Y. – PersonEntity: Name: NameFull: Trakselis, Michael A. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 11 Text: Nov2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 301 – Type: issue Value: 11 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
