Replication Protein A is a single-stranded (ss) DNA-binding protein that is highly conserved in eukaryotes and plays essential roles in many aspects of nucleic acid metabolism, including replication, recombination, DNA repair and telomere maintenance. It is a heterotrimeric complex consisting of three subunits: RPA1, RPA2 and RPA3. It possesses four DNA-binding domains (DBD), DBD-A, DBD-B and DBD-C in RPA1 and DBD-D in RPA2, and it binds ssDNA via a multistep pathway. Unlike the RPA1 and RPA2 subunits, no ssDNA-RPA3 interaction has as yet been observed although RPA3 contains a structural motif found in the other DBDs. We show here using 4-thiothymine residues as photoaffinity probe that RPA3 interacts directly with ssDNA on the 3'-side on a 31 nt ssDNA.
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http://dx.doi.org/10.1093/nar/gkn895 | DOI Listing |
FASEB J
January 2025
State Key Laboratory of Virology, Institute of Medical Virology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, Hubei, China.
Hantaan virus (HTNV) infection causes severe hemorrhagic fever with renal syndrome (HFRS) in humans and the infectious process can be regulated by autophagy. The phosphatase and tensin homolog (PTEN) protein has antiviral effects and plays a critical role in the autophagy pathway. However, the relationship between PTEN and HTNV infection is not clear and whether PTEN-regulated autophagy involves in HTNV replication is unknown.
View Article and Find Full Text PDFJ Virol
January 2025
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Coronaviruses (CoVs) encode non-structural proteins (nsp's) 1-16, which assemble to form replication-transcription complexes that function in viral RNA synthesis. All CoVs encode a proofreading 3'-5' exoribonuclease in non-structural protein 14 (nsp14-ExoN) that mediates proofreading and high-fidelity replication and is critical for other roles in replication and pathogenesis. The enzymatic activity of nsp14-ExoN is enhanced in the presence of the cofactor nsp10.
View Article and Find Full Text PDFJ Virol
January 2025
Department of Host-Microbe Interactions, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Unlabelled: The tonsils have been identified as a site of replication for Epstein-Barr virus, adenovirus, human papillomavirus, and other respiratory viruses. Human tonsil epithelial cells (HTECs) are a heterogeneous group of actively differentiating cells. Here, we investigated the cellular features and susceptibility of differentiated HTECs to specific influenza viruses, including expression of avian-type and mammalian-type sialic acid (SA) receptors, viral replication dynamics, and the associated cytokine secretion profiles.
View Article and Find Full Text PDFCells
January 2025
Biotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, Denmark.
Nuclear actin polymerization was reported to control different nuclear processes, but its regulation is poorly understood. Here, we show that N-WASP can trigger the formation of nuclear N-WASP/F-actin nodules. While a cancer hotspot mutant of N-WASP lacking the VCA domain (V418fs) had a dominant negative function on nuclear F-actin, an even shorter truncation mutant found in melanoma (R128*) strongly promoted nuclear actin polymerization.
View Article and Find Full Text PDFCells
December 2024
Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, 4100 John R Street, Detroit, MI 48201, USA.
The DNA replication machinery is highly conserved from bacteria to eukaryotic cells. Faithful DNA replication is vital for cells to transmit accurate genetic information to the next generation. However, both internal and external DNA damages threaten the intricate DNA replication process, leading to the activation of the DNA damage response (DDR) system.
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