RAD51 Gene Family Structure and Function

Accurate DNA repair and replication are critical for genomic stability and cancer prevention. RAD51 and its gene family are key regulators of DNA fidelity through diverse roles in double-strand break repair, replication stress, and meiosis. RAD51 is an ATPase that forms a nucleoprotein filament on single-stranded DNA. RAD51 has the function of finding and invading homologous DNA sequences to enable accurate and timely DNA repair. Its paralogs, which arose from ancient gene duplications of RAD51, have evolved to regulate and promote RAD51 function. Underscoring its importance, misregulation of RAD51, and its paralogs, is associated with diseases such as cancer and Fanconi anemia. In this review, we focus on the mammalian RAD51 structure and function and highlight the use of model systems to enable mechanistic understanding of RAD51 cellular roles. We also discuss how misregulation of the RAD51 gene family members contributes to disease and consider new approaches to pharmacologically inhibit RAD51.

Download Full-text

Islands of complex DNA are widespread in Drosophila centric heterochromatin.

Genetics ◽

10.1093/genetics/141.1.283 ◽

1995 ◽

Vol 141 (1) ◽

pp. 283-303

Author(s):

M H Le ◽

D Duricka ◽

G H Karpen

Keyword(s):

Dna Sequences ◽

Structure And Function ◽

Southern Analysis ◽

Cloning And Sequencing ◽

Pulsed Field ◽

Drosophila Heterochromatin ◽

And Function ◽

Heterochromatin Structure ◽

Derivatives Of ◽

Eukaryotic Genomes

Abstract Heterochromatin is a ubiquitous yet poorly understood component of multicellular eukaryotic genomes. Major gaps exist in our knowledge of the nature and overall organization of DNA sequences present in heterochromatin. We have investigated the molecular structure of the 1 Mb of centric heterochromatin in the Drosophila minichromosome Dp1187. A genetic screen of irradiated minichromosomes yielded rearranged derivatives of Dp1187 whose structures were determined by pulsed-field Southern analysis and PCR. Three Dp1187 deletion derivatives and an inversion had one breakpoint in the euchromatin and one in the heterochromatin, providing direct molecular access to previously inaccessible parts of the heterochromatin. End-probed pulsed-field restriction mapping revealed the presence of at least three "islands" of complex DNA, Tahiti, Moorea, and Bora Bora, constituting approximately one half of the Dp1187 heterochromatin. Pulsed-field Southern analysis demonstrated that Drosophila heterochromatin in general is composed of alternating blocks of complex DNA and simple satellite DNA. Cloning and sequencing of a small part of one island, Tahiti, demonstrated the presence of a retroposon. The implications of these findings to heterochromatin structure and function are discussed.

Download Full-text

DNAContentViewer a BioJS component to visualise GC/AT Content

F1000Research ◽

10.12688/f1000research.3-54.v1 ◽

2014 ◽

Vol 3 ◽

pp. 54 ◽

Cited By ~ 1

Author(s):

Anil S. Thanki ◽

Shabhonam Caim ◽

Manuel Corpas ◽

Robert P. Davey

Keyword(s):

Dna Sequences ◽

Genome Analysis ◽

Biological Function ◽

Structure And Function ◽

Link Type ◽

And Function ◽

Potential Interactions

Summary: Compositional GC/AT content of DNA sequences is a useful feature in genome analysis. GC/AT content provides useful information about evolution, structure and function of genomes, giving clues about their biological function and organisation. We have developed DNAContentViewer, a BioJS component for visualisation of compositional GC/AT content in raw sequences. DNAContentViewer has been integrated in the BioJS project as part of the BioJS registry of components. DNAContentViewer requires a simple configuration and installation. Its design allows potential interactions with other components via predefined events. Availability: http://github.com/biojs/biojs; doi: 10.5281/zenodo.7722.

Download Full-text

Control of Metal Nanocrystal Size Reveals Metal-Support Interface Role for Ceria Catalysts

Science ◽

10.1126/science.1240148 ◽

2013 ◽

Vol 341 (6147) ◽

pp. 771-773 ◽

Cited By ~ 725

Author(s):

Matteo Cargnello ◽

Vicky V. T. Doan-Nguyen ◽

Thomas R. Gordon ◽

Rosa E. Diaz ◽

Eric A. Stach ◽

...

Keyword(s):

Carbon Monoxide ◽

Structure And Function ◽

Nanocrystal Size ◽

Model Systems ◽

Group Viii ◽

Metal Interface ◽

Platinum Nanocrystals ◽

Metal Support ◽

Ceria Catalysts ◽

And Function

Interactions between ceria (CeO2) and supported metals greatly enhance rates for a number of important reactions. However, direct relationships between structure and function in these catalysts have been difficult to extract because the samples studied either were heterogeneous or were model systems dissimilar to working catalysts. We report rate measurements on samples in which the length of the ceria-metal interface was tailored by the use of monodisperse nickel, palladium, and platinum nanocrystals. We found that carbon monoxide oxidation in ceria-based catalysts is greatly enhanced at the ceria-metal interface sites for a range of group VIII metal catalysts, clarifying the pivotal role played by the support.

Download Full-text

The VEGF receptor neuropilin 2 promotes homologous recombination by stimulating YAP/TAZ-mediated Rad51 expression

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1821194116 ◽

2019 ◽

Vol 116 (28) ◽

pp. 14174-14180 ◽

Cited By ~ 8

Author(s):

Ameer L. Elaimy ◽

John J. Amante ◽

Lihua Julie Zhu ◽

Mengdie Wang ◽

Charlotte S. Walmsley ◽

...

Keyword(s):

Dna Repair ◽

Homologous Recombination ◽

Strand Break ◽

Vegf Receptor ◽

Vegf Signaling ◽

Dna Double Strand Break ◽

Essential Enzyme ◽

And Function ◽

Platinum Chemotherapy ◽

Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) signaling in tumor cells mediated by neuropilins (NRPs) contributes to the aggressive nature of several cancers, including triple-negative breast cancer (TNBC), independently of its role in angiogenesis. Understanding the mechanisms by which VEGF–NRP signaling contributes to the phenotype of such cancers is a significant and timely problem. We report that VEGF–NRP2 promote homologous recombination (HR) in BRCA1 wild-type TNBC cells by contributing to the expression and function of Rad51, an essential enzyme in the HR pathway that mediates efficient DNA double-strand break repair. Mechanistically, we provide evidence that VEGF–NRP2 stimulates YAP/TAZ-dependent Rad51 expression and that Rad51 is a direct YAP/TAZ–TEAD transcriptional target. We also discovered that VEGF–NRP2–YAP/TAZ signaling contributes to the resistance of TNBC cells to cisplatin and that Rad51 rescues the defects in DNA repair upon inhibition of either VEGF–NRP2 or YAP/TAZ. These findings reveal roles for VEGF–NRP2 and YAP/TAZ in DNA repair, and they indicate a unified mechanism involving VEGF–NRP2, YAP/TAZ, and Rad51 that contributes to resistance to platinum chemotherapy.

Download Full-text

Chromatin-Mediated Regulation of Genome Plasticity in Human Fungal Pathogens

Genes ◽

10.3390/genes10110855 ◽

2019 ◽

Vol 10 (11) ◽

pp. 855 ◽

Cited By ~ 3

Author(s):

Buscaino

Keyword(s):

Candida Albicans ◽

Aspergillus Fumigatus ◽

Cryptococcus Neoformans ◽

Fungal Pathogens ◽

Environmental Changes ◽

Structure And Function ◽

Model Systems ◽

Genome Plasticity ◽

And Function ◽

Heterochromatin Structure

Human fungal pathogens, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, are a public health problem, causing millions of infections and killing almost half a million people annually. The ability of these pathogens to colonise almost every organ in the human body and cause life-threating infections relies on their capacity to adapt and thrive in diverse hostile host-niche environments. Stress-induced genome instability is a key adaptive strategy used by human fungal pathogens as it increases genetic diversity, thereby allowing selection of genotype(s) better adapted to a new environment. Heterochromatin represses gene expression and deleterious recombination and could play a key role in modulating genome stability in response to environmental changes. However, very little is known about heterochromatin structure and function in human fungal pathogens. In this review, I use our knowledge of heterochromatin structure and function in fungal model systems as a road map to review the role of heterochromatin in regulating genome plasticity in the most common human fungal pathogens: Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans.

Download Full-text