Early B-cell factor 1 (Ebf1) is a key transcriptional determinant of B-lymphocyte differentiation whose DNA-binding domain has no sequence similarity to other transcription factor families. Here we report the crystal structure of an Ebf1 dimer bound to its palindromic recognition site. The DNA-binding domain adopts a pseudoimmunoglobulin-like fold with novel topology, but is structurally similar to the Rel homology domains of NFAT and NF-κB. Ebf1 contacts the DNA with two loop-based modules and a unique Zn coordination motif whereby each Ebf1 monomer interacts with both palindromic half-sites. This unusual mode of DNA recognition generates an extended contact area that may be crucial for the function of Ebf1 in chromatin.
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http://dx.doi.org/10.1101/gad.1976610 | DOI Listing |
J Biomed Sci
January 2025
Key Laboratory of Molecular Epigenetics of Ministry of Education, College of Life Sciences, Northeast Normal University, Changchun, 130024, China.
ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product of guanine, is one of the most abundant. If left unrepaired, 8-oxoGua may pair with A instead of C, leading to a mutation of G: C to T: A during DNA replication. 8-Oxoguanine DNA glycosylase 1 (OGG1) is a tailored repair enzyme that recognizes 8-oxoGua in DNA duplex and initiates the base excision repair (BER) pathway to remove the lesion and ensure the fidelity of the genome.
View Article and Find Full Text PDFBiosens Bioelectron
December 2024
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China. Electronic address:
"One-pot" assays which combine amplification with CRISPR/Cas12a system are in constant attracted for biosensors development. Herein, we present a one-pot isothermal assay that Ligation-recognition triggered Recombinase Polymerase Amplification (RPA)-CRISPR/Cas12a cis-cleavage (LRPA-CRISPR) fluorescent biosensor for sensitive, specific, and label-free miRNA detection. Firstly, we reveal the programmed double-stranded DNA amplicons, which utilized the ligation-recognition and polymerization to form and amplified by the RPA system.
View Article and Find Full Text PDFChem Asian J
December 2024
Guangxi Normal University, School of chemistry and pharmaceutical science, No.15, Yucai Road, 541004, Guilin, CHINA.
The anomalous expression of microRNA poses a serious threat to human life and health safety, and serves as an important biomarker for cancer detection. In this study, a novel magnetic-assisted DNA logic gate nanomachine triggered by miRNA-21 and miRNA-155 was designed based on the trans-cleavage activity of CRISPR/Cas12a activated by a split DNA activator, using only a single crRNA and signal probe, which simplified the detection procedure and complex nucleic acid amplification. The presence of target molecules, miRNA-21 and miRNA-155, can stimulate the DNA walker machine assembled on magnetic beads, which releases activator under the action of DNAzyme.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-5222.
Tsg101 is a highly conserved protein best known as an early-functioning component of cellular ESCRT machinery participating in recognition, sorting, and trafficking of cellular cargo to various intracellular destinations. It shares sequence and structural homology to canonical ubiquitin-conjugating (E2) enzymes and is linked to diverse events regulated by Ub signaling. How it might fulfill these roles is unclear.
View Article and Find Full Text PDFPLoS One
December 2024
Neuroscience, Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey, United States of America.
Ataxin-2 is a protein containing a polyQ extension and intermediate length of polyQ extensions increases the risk of Amyotrophic Lateral Sclerosis (ALS). Down-regulation of Ataxin-2 has been shown to mitigate TDP-43 proteinopathy in ALS models. To identify alternative therapeutic targets that can mitigate TDP-43 toxicity, we examined the interaction between Ataxin-2 and TDP-43.
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