Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Replication Protein A (RPA), the major eukaryotic single stranded DNA-binding protein, binds to exposed ssDNA to protect it from nucleases, participates in a myriad of nucleic acid transactions and coordinates the recruitment of other important players. RPA is a heterotrimer and coats long stretches of single-stranded DNA (ssDNA). The precise molecular architecture of the RPA subunits and its DNA binding domains (DBDs) during assembly is poorly understood. Using cryo electron microscopy we obtained a 3D reconstruction of the RPA trimerisation core bound with ssDNA (∼55 kDa) at ∼4.7 Å resolution and a dimeric RPA assembly on ssDNA. FRET-based solution studies reveal dynamic rearrangements of DBDs during coordinated RPA binding and this activity is regulated by phosphorylation at S178 in RPA70. We present a structural model on how dynamic DBDs promote the cooperative assembly of multiple RPAs on long ssDNA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303327 | PMC |
| http://dx.doi.org/10.1038/s41467-018-07883-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Serotonergic receptor binding in the brainstem in the Sudden Infant Death Syndrome in a high-risk population.
PLoS One
September 2025
Department of Pathology, Boston Children's Hospital, Harvard School of Medicine, Boston, Massachusetts, United States of America.
The Sudden Infant Death Syndrome (SIDS) is a major global health problem, with increased risk among socioeconomically disadvantaged populations. We propose SIDS, or a subset, is due to a defect in the brainstem serotonin system mediating cardiorespiratory integration and arousal. This defect impinges on homeostasis during a critical developmental period in infancy, especially in populations experiencing maternal and infantile stress, resulting in sleep-related sudden death.
View Article and Find Full Text PDFDNA polymerase α-primase can function as a translesion DNA polymerase.
Proc Natl Acad Sci U S A
September 2025
HHMI and The Rockefeller University, New York, NY 10065.
Replication of cellular chromosomes requires a primase to generate short RNA primers to initiate genomic replication. While bacterial and archaeal primase generate short RNA primers, the eukaryotic primase, Polα-primase, contains both RNA primase and DNA polymerase (Pol) subunits that function together to form a >20 base hybrid RNA-DNA primer. Interestingly, the DNA Pol1 subunit of Polα lacks a 3'-5' proofreading exonuclease, contrary to the high-fidelity normally associated with DNA replication.
View Article and Find Full Text PDFReplication stress-induced nuclear hypertrophy alters chromatin topology and impacts cancer cell fitness.
Proc Natl Acad Sci U S A
September 2025
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34051, Republic of Korea.
Microscopic examination of biopsy tissues remains essential for cancer diagnosis, despite advancements in sequencing technologies. Alterations in nuclear size or the nuclear-to-cytoplasmic ratio are hallmark features of cancer cells and often correlate with disease progression. However, the mechanisms underlying nuclear size abnormalities and their impact on tumor progression remain unclear.
View Article and Find Full Text PDFThe RecBC complex protects single-stranded DNA gaps during lesion bypass.
Proc Natl Acad Sci U S A
September 2025
Cancer Research Center of Marseille: Team DNA Damage and Genome Instability|CNRS, Inserm, Institut Paoli-Calmettes, Aix Marseille Université, Marseille 13009, France.
Following encounter with an unrepaired DNA lesion, replication is halted and can restart downstream of the lesion leading to the formation of a single-stranded DNA (ssDNA) gap. To complete replication, this ssDNA gap is filled in by one of the two lesion tolerance pathways: the error-prone Translesion Synthesis (TLS) or the error-free Homology Directed Gap Repair (HDGR). In the present work, we evidence a role for the RecBC complex distinct from its canonical function in homologous recombination at DNA double strand breaks.
View Article and Find Full Text PDFThe mammalian SKI complex is a broad-spectrum antiviral drug target that upregulates cellular cholesterol to inhibit viral replication.
J Virol
September 2025
Department of Microbiology and Immunology, Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Unlabelled: There is a need for the development of broad-spectrum antiviral compounds that can act as first-line therapeutic countermeasures to emerging viral infections. Host-directed approaches present a promising avenue of development and carry the benefit of mitigating risks of viral escape mutants. We have previously found the SKI (super killer) complex to be a broad-spectrum, host-target with our lead compound ("UMB18") showing activity against influenza A virus, coronaviruses, and filoviruses.
View Article and Find Full Text PDF