Single-stranded overhangs of the G-rich strand belong to the conserved features of telomeres composed of short telomeric repeats. These structures are thought to be essential for the maintenance of proper telomeric structure and function and the mechanism of their generation is telomerase-independent. We have examined the presence of single-stranded overhangs in Chironomus tentans, a dipteran insect lacking canonical telomeres that uses 350-bp repeats to terminate its chromosomes. Using a non-denaturing in-gel hybridization technique, we found that C. tentans telomeres are unlikely to have single-stranded overhangs longer than 30 nt found in most other higher eukaryotes. These differences might reflect special capping mechanisms for telomeres terminated with long complex repeats.
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http://dx.doi.org/10.1023/a:1014257808705 | DOI Listing |
J Phys Chem B
January 2025
College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG(TAG)) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K or Na solution (i.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
The regressed arms of reversed replication forks exhibit structural similarities to one-ended double-stranded breaks and need to be protected against uncontrolled nucleolytic degradation. Here, we identify MSANTD4 (Myb/SANT-like DNA-binding domain-containing protein 4), a functionally uncharacterized protein that uniquely counters the replication protein A (RPA)-Bloom (BLM)/Werner syndrome helicase (WRN)-DNA replication helicase/nuclease 2 (DNA2) complex to safeguard reversed replication forks from detrimental degradation, independently of the breast cancer susceptibility proteins (BRCA1/2)-DNA repair protein RAD51 pathway. MSANTD4 specifically interacts with the junctions between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in DNA substrates harboring a 3' overhang, which resemble the structural features of regressed arms processed by WRN-DNA2.
View Article and Find Full Text PDFMol Cell
December 2024
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA. Electronic address:
Prokaryotes possess diverse anti-bacteriophage immune systems, including the single-protein Shedu nuclease. Here, we reveal the structural basis for activation of Bacillus cereus Shedu. Two cryoelectron microscopy structures of Shedu show that it switches between inactive and active states through conformational changes affecting active-site architecture, which are controlled by the protein's N-terminal domain (NTD).
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.
Homologous recombination (HR) is the principal pathway undertaken by a cell for the error-free repair of DNA double-strand breaks that are frequently encountered by the cell. HR can be initiated at the sites of DNA double-strand breaks by generating long stretches of single-stranded 3' DNA overhang through a process called DNA end resection. In one DNA end resection pathway, this is achieved via the concerted effort of specialized machinery involving the RecQ family helicase BLM, the helicase/endonuclease DNA2, and a single-strand DNA binding protein complex RPA.
View Article and Find Full Text PDFSmall
January 2025
Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin, 300071, China.
With sequence-programmable biological functions and excellent biocompatibility, synthetic functional DNA holds great promise for various biological applications. However, it remains a challenge to simultaneously retain their biological functions while protecting these fragile oligonucleotides from the degradation by nucleases abundant in biological circumstances. Herein, a smart delivery system for functional DNA payloads is developed based on proton-mediated dynamic nestling of cytosine-rich DNA moieties within the precisely size-matched nanochannels of highly crystalline metal-organic frameworks (MOFs): At neutral pH, cytosine-rich DNA strands exhibit a flexible single-stranded state and can be accommodated by MOFs nanochannels with a size of ca.
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