Structural insights into sequence-dependent Holliday junction resolution by the chloroplast resolvase MOC1

Yan, Junjie; Hong, Sixing; Guan, Zeyuan; He, Wenjing; Zhang, Delin; Yin, Ping

doi:10.1038/s41467-020-15242-8

Cited by 12 publications

(9 citation statements)

References 56 publications

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“…Epigenetic markers on DNA, such as hydroxymethyl and methyl substituents, can be accommodated without disrupting the structure or stability of the cruciform, although they open the structure to make the junction core more accessible [ 36 ]. The binding of proteins—usually enzymes—to four-way junctions can alter their conformation, although they can have dramatically different effects [ 36 , 39 , 40 , 41 ]. High-resolution structures that are currently available for these altered conformations of four-way DNA junctions with proteins bound are usually for sequences that are not inverted repeats.…”

Section: Biophysical and Molecular Characterization Of Cruciformsmentioning

confidence: 99%

Interaction of Proteins with Inverted Repeats and Cruciform Structures in Nucleic Acids

Bowater

Bohálová

Brázda

2022

IJMS

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Cruciforms occur when inverted repeat sequences in double-stranded DNA adopt intra-strand hairpins on opposing strands. Biophysical and molecular studies of these structures confirm their characterization as four-way junctions and have demonstrated that several factors influence their stability, including overall chromatin structure and DNA supercoiling. Here, we review our understanding of processes that influence the formation and stability of cruciforms in genomes, covering the range of sequences shown to have biological significance. It is challenging to accurately sequence repetitive DNA sequences, but recent advances in sequencing methods have deepened understanding about the amounts of inverted repeats in genomes from all forms of life. We highlight that, in the majority of genomes, inverted repeats are present in higher numbers than is expected from a random occurrence. It is, therefore, becoming clear that inverted repeats play important roles in regulating many aspects of DNA metabolism, including replication, gene expression, and recombination. Cruciforms are targets for many architectural and regulatory proteins, including topoisomerases, p53, Rif1, and others. Notably, some of these proteins can induce the formation of cruciform structures when they bind to DNA. Inverted repeat sequences also influence the evolution of genomes, and growing evidence highlights their significance in several human diseases, suggesting that the inverted repeat sequences and/or DNA cruciforms could be useful therapeutic targets in some cases.

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Section: Biophysical and Molecular Characterization Of Cruciformsmentioning

confidence: 99%

Interaction of Proteins with Inverted Repeats and Cruciform Structures in Nucleic Acids

Bowater

Bohálová

Brázda

2022

IJMS

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“…Holliday junctions (HJs) are noncanonical DNA structures with four joined duplexes (Figure ). , The formation of HJs is the cornerstone of homologous recombination, yielding a motif prominent in DNA repair and meiosis. , Accurate recognition of HJs by proteins ensures stable genetic information processing, while their ability for branch migration or base pair exchange in homologous DNA regions allows for genetic variety. − The cross-like conformation of HJs is also a widely utilized tool in nanomaterial science where it is the basic structural unit for building DNA nanostructures such as DNA crystals, tiles, and origamis. − …”

Section: Introductionmentioning

confidence: 99%

Atomistic Picture of Opening–Closing Dynamics of DNA Holliday Junction Obtained by Molecular Simulations

Zhang

Šponer

Bussi

et al. 2023

J. Chem. Inf. Model.

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Holliday junction (HJ) is a noncanonical four-way DNA structure with a prominent role in DNA repair, recombination, and DNA nanotechnology. By rearranging its four arms, HJ can adopt either closed or open state. With enzymes typically recognizing only a single state, acquiring detailed knowledge of the rearrangement process is an important step toward fully understanding the biological function of HJs. Here, we carried out standard all-atom molecular dynamics (MD) simulations of the spontaneous opening–closing transitions, which revealed complex conformational transitions of HJs with an involvement of previously unconsidered “half-closed” intermediates. Detailed free-energy landscapes of the transitions were obtained by sophisticated enhanced sampling simulations. Because the force field overstabilizes the closed conformation of HJs, we developed a system-specific modification which for the first time allows the observation of spontaneous opening–closing HJ transitions in unbiased MD simulations and opens the possibilities for more accurate HJ computational studies of biological processes and nanomaterials.

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“…As a transient DNA intermediate, HJ performs its biological function mainly relying on conformational variation [ 12 ]. Generally, HJ generally has two configurations: “X-stacked” and “open-planar” ( Figure 1 B) [ 13 , 14 , 15 ]. In the presence of low salt concentrations, the “open-planar” state is a predominant configuration; otherwise, the junction can be transformed to a symmetric X-shape termed “X-stacked” at higher ionic concentrations.…”

Section: Introductionmentioning

confidence: 99%

DNA Holliday Junction: History, Regulation and Bioactivity

Song

Yin

et al. 2022

IJMS

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DNA Holliday junction (HJ) is a four-way stranded DNA intermediate that formed in replication fork regression, homology-dependent repair and mitosis, performing a significant role in genomic stability. Failure to remove HJ can induce an acceptable replication fork stalling and DNA damage in normal cells, leading to a serious chromosomal aberration and even cell death in HJ nuclease-deficient tumor cells. Thus, HJ is becoming an attractive target in cancer therapy. However, the development of HJ-targeting ligand faces great challenges because of flexile cavities on the center of HJs. This review introduces the discovery history of HJ, elucidates the formation and dissociation procedures of HJ in corresponding bio-events, emphasizes the importance of prompt HJ-removing in genome stability, and summarizes recent advances in HJ-based ligand discovery. Our review indicate that target HJ is a promising approach in oncotherapy.

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Structural insights into sequence-dependent Holliday junction resolution by the chloroplast resolvase MOC1

Cited by 12 publications

References 56 publications

Interaction of Proteins with Inverted Repeats and Cruciform Structures in Nucleic Acids

Interaction of Proteins with Inverted Repeats and Cruciform Structures in Nucleic Acids

Atomistic Picture of Opening–Closing Dynamics of DNA Holliday Junction Obtained by Molecular Simulations

DNA Holliday Junction: History, Regulation and Bioactivity

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