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Binding of Homeodomain Proteins to DNA with Hoogsteen Base Pair.
J Phys Chem B
January 2025
Department of Physics of Complex Systems, S. N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata 700106, India.
In DNA double helices, Hoogsteen (HG) base pairing is an alternative mode of Watson-Crick (WC) base pairing. HG bp has a different hydrogen bonding pattern than WC bp. We investigate here the binding energy of homeodomain proteins with a HG-DNA duplex, where DNA adopts a HG bp in its sequence.
View Article and Find Full Text PDFMultiscale footprints reveal the organization of cis-regulatory elements.
Nature
January 2025
Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.
View Article and Find Full Text PDFBIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation.
World J Gastrointest Oncol
January 2025
Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high morbidity and mortality, and easy to develop resistance to chemotherapeutic agents. Telomeres are DNA-protein complexes located at the termini of chromosomes in eukaryotic cells, which are unreplaceable in maintaining the stability and integrity of genome. Telomerase, an RNA-dependent DNA polymerase, play vital role in telomere length maintain, targeting telomerase is a promising therapeutic strategy for cancer.
View Article and Find Full Text PDFSingle-cell mapping of regulatory DNA:Protein interactions.
bioRxiv
January 2025
Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Gene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells.
View Article and Find Full Text PDFSPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.
Sci Rep
December 2024
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.
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