Lagging Strand Initiation Processes in DNA Replication of Eukaryotes—Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes
In their influential reviews, Hanahan and Weinberg coined the term ‘Hallmarks of Cancer’ and described genome instability as a property of cells enabling cancer development. Accurate DNA replication of genomes is central to diminishing genome instability. Here, the understanding of the initiation of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/5/1012 |
| _version_ | 1797600011829116928 |
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| author | Heinz Peter Nasheuer Nichodemus O. Onwubiko |
| author_facet | Heinz Peter Nasheuer Nichodemus O. Onwubiko |
| author_sort | Heinz Peter Nasheuer |
| collection | DOAJ |
| description | In their influential reviews, Hanahan and Weinberg coined the term ‘Hallmarks of Cancer’ and described genome instability as a property of cells enabling cancer development. Accurate DNA replication of genomes is central to diminishing genome instability. Here, the understanding of the initiation of DNA synthesis in origins of DNA replication to start leading strand synthesis and the initiation of Okazaki fragment on the lagging strand are crucial to control genome instability. Recent findings have provided new insights into the mechanism of the remodelling of the prime initiation enzyme, DNA polymerase α-primase (Pol-prim), during primer synthesis, how the enzyme complex achieves lagging strand synthesis, and how it is linked to replication forks to achieve optimal initiation of Okazaki fragments. Moreover, the central roles of RNA primer synthesis by Pol-prim in multiple genome stability pathways such as replication fork restart and protection of DNA against degradation by exonucleases during double-strand break repair are discussed. |
| first_indexed | 2024-03-11T03:42:27Z |
| format | Article |
| id | doaj.art-35f257a06d6a4c7ba738b1b422ea5c4d |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T03:42:27Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-35f257a06d6a4c7ba738b1b422ea5c4d2023-11-18T01:29:14ZengMDPI AGGenes2073-44252023-04-01145101210.3390/genes14051012Lagging Strand Initiation Processes in DNA Replication of Eukaryotes—Strings of Highly Coordinated Reactions Governed by Multiprotein ComplexesHeinz Peter Nasheuer0Nichodemus O. Onwubiko1Centre for Chromosome Biology, Arts & Science Building, Main Concourse, School of Biological and Chemical Sciences, Biochemistry, University of Galway, Distillery Road, H91 TK33 Galway, IrelandCentre for Chromosome Biology, Arts & Science Building, Main Concourse, School of Biological and Chemical Sciences, Biochemistry, University of Galway, Distillery Road, H91 TK33 Galway, IrelandIn their influential reviews, Hanahan and Weinberg coined the term ‘Hallmarks of Cancer’ and described genome instability as a property of cells enabling cancer development. Accurate DNA replication of genomes is central to diminishing genome instability. Here, the understanding of the initiation of DNA synthesis in origins of DNA replication to start leading strand synthesis and the initiation of Okazaki fragment on the lagging strand are crucial to control genome instability. Recent findings have provided new insights into the mechanism of the remodelling of the prime initiation enzyme, DNA polymerase α-primase (Pol-prim), during primer synthesis, how the enzyme complex achieves lagging strand synthesis, and how it is linked to replication forks to achieve optimal initiation of Okazaki fragments. Moreover, the central roles of RNA primer synthesis by Pol-prim in multiple genome stability pathways such as replication fork restart and protection of DNA against degradation by exonucleases during double-strand break repair are discussed.https://www.mdpi.com/2073-4425/14/5/1012genome stabilityDNA replicationlagging strand DNA synthesisOkazaki fragmentsinitiationDNA polymerase α |
| spellingShingle | Heinz Peter Nasheuer Nichodemus O. Onwubiko Lagging Strand Initiation Processes in DNA Replication of Eukaryotes—Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes Genes genome stability DNA replication lagging strand DNA synthesis Okazaki fragments initiation DNA polymerase α |
| title | Lagging Strand Initiation Processes in DNA Replication of Eukaryotes—Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes |
| title_full | Lagging Strand Initiation Processes in DNA Replication of Eukaryotes—Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes |
| title_fullStr | Lagging Strand Initiation Processes in DNA Replication of Eukaryotes—Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes |
| title_full_unstemmed | Lagging Strand Initiation Processes in DNA Replication of Eukaryotes—Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes |
| title_short | Lagging Strand Initiation Processes in DNA Replication of Eukaryotes—Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes |
| title_sort | lagging strand initiation processes in dna replication of eukaryotes strings of highly coordinated reactions governed by multiprotein complexes |
| topic | genome stability DNA replication lagging strand DNA synthesis Okazaki fragments initiation DNA polymerase α |
| url | https://www.mdpi.com/2073-4425/14/5/1012 |
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