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Biomolecules
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Roles of DNA Topology and Topoisomerases in Transcription, DNA Replication,...
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Roles of DNA Topology and Topoisomerases in Transcription, DNA Replication, Chromosome Structure, and Genomic Stability

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Enzymology".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 4655

Special Issue Editor

Dr. Fenfei Leng

E-Mail Website
Guest Editor
Biomolecular Sciences Institute and Department of Chemistry & Biochemistry, College of Arts, Sciences & Education, Florida International University, Miami, 33199 FL, USA
Interests: DNA topology; DNA topoisomerases; transcription; protein-DNA interactions; HMGA2

Special Issue Information

Dear Colleagues,

DNA topology or supercoiling is a unique and fundamental property of DNA double helix. Typically, DNA in live cells is negatively supercoiled. Free energy constrained in negative supercoils has significant biological consequences and usually promotes essential DNA processes such as transcription and DNA replication. DNA topology also greatly affects chromosome structure and genomic stability. Furthermore, DNA polymerase and RNA polymerase, when replicating or transcribing along the DNA double helix, induce superhelical changes to the DNA molecules. Leroy F. Liu and James C. Wang formulated an elegant twin-supercoiled domain model to explain transcription-induced DNA supercoiling: a transcribing RNA polymerase becomes progressively more difficult to rotate around the DNA double helix as the size of the growing RNA transcript increases. At a critical point, energetically, it is more feasible for the DNA molecule to rotate around its own helical axis to produce a positively supercoiled domain in front of the RNA polymerase and a negatively supercoiled domain behind it. Many experimental evidences demonstrated the importance of this dynamic supercoiling.

DNA topoisomerases, discovered half a century ago by James C. Wang, are essential enzymes to all living organisms. These enzymes resolve the DNA topological issues arisen from DNA replication and transcription usually through relaxing positive and negative DNA supercoiling generated from these processes. Therefore, DNA topoisomerases are critical for DNA replication, transcription, and maintenance of the chromosome structure. Because of their importance, DNA topoisomerases are the targets of certain clinically important antibiotics and anticancer drugs.

The aim of this special issue is to provide a forum to discuss the importance of DNA topology and topoisomerases in transcription, DNA replication, chromosome structure, and genomic stability. Original article and reviews are welcome.

Dr. Fenfei Leng
Guest Editor

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Keywords

  • DNA topology or supercoiling
  • DNA topoisomerase
  • DNA replication and transcription
  • chromosome
  • genomic stability

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Published Papers (1 paper)

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Research

17 pages, 1842 KiB  
Article
Interaction of the Escherichia coli HU Protein with Various Topological Forms of DNA
by Li Huang, Zhenfeng Zhang and Roger McMacken
Biomolecules 2021, 11(11), 1724; https://doi.org/10.3390/biom11111724 - 19 Nov 2021
Cited by 9 | Viewed by 3093
Abstract
E. coli histone-like protein HU has been shown to interact with different topological forms of DNA. Using radiolabeled HU, we examine the effects of DNA supercoiling on HU–DNA interactions. We show that HU binds preferentially to negatively supercoiled DNA and that the affinity [...] Read more.
E. coli histone-like protein HU has been shown to interact with different topological forms of DNA. Using radiolabeled HU, we examine the effects of DNA supercoiling on HU–DNA interactions. We show that HU binds preferentially to negatively supercoiled DNA and that the affinity of HU for DNA increases with increases in the negative superhelical density of DNA. Binding of HU to DNA is most sensitively influenced by DNA supercoiling within a narrow but physiologically relevant range of superhelicity (σ = −0.06–0). Under stoichiometric binding conditions, the affinity of HU for negatively supercoiled DNA (σ = −0.06) is more than 10 times higher than that for relaxed DNA at physiologically relevant HU/DNA mass ratios (e.g., 1:10). This binding preference, however, becomes negligible at HU/DNA mass ratios higher than 1:2. At saturation, HU binds both negatively supercoiled and relaxed DNA with similar stoichiometries, i.e., 5–6 base pairs per HU dimer. In our chemical crosslinking studies, we demonstrate that HU molecules bound to negatively supercoiled DNA are more readily crosslinked than those bound to linear DNA. At in vivo HU/DNA ratios, HU appears to exist predominantly in a tetrameric form on negatively supercoiled DNA and in a dimeric form on linear DNA. Using a DNA ligase-mediated nick closure assay, we show that approximately 20 HU dimers are required to constrain one negative supercoil on relaxed DNA. Although fewer HU dimers may be needed to constrain one negative supercoil on negatively supercoiled DNA, our results and estimates of the cellular level of HU argue against a major role for HU in constraining supercoils in vivo. We discuss our data within the context of the dynamic distribution of the HU protein in cells, where temporal and local changes of DNA supercoiling are known to take place. Full article
(This article belongs to the Special Issue Roles of DNA Topology and Topoisomerases in Transcription, DNA Replication, Chromosome Structure, and Genomic Stability)
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