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Defective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer.
NPJ Precis Oncol
January 2025
Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Pancreatic ductal adenocarcinoma (PDAC) is notably resistant to conventional chemotherapy and radiation treatment. However, clinical trials indicate that carbon ion radiotherapy (CIRT) with concurrent gemcitabine is effective for unresectable locally advanced PDAC. This study aimed to identify patient characteristics predictive of CIRT response.
View Article and Find Full Text PDFCase-Based Virtual Reality Simulation for Severe Pelvic Trauma Clinical Skill Training in Medical Students: Design and Pilot Study.
JMIR Med Educ
January 2025
Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Background: Teaching severe pelvic trauma poses a significant challenge in orthopedic surgery education due to the necessity of both clinical reasoning and procedural operational skills for mastery. Traditional methods of instruction, including theoretical teaching and mannequin practice, face limitations due to the complexity, the unpredictability of treatment scenarios, the scarcity of typical cases, and the abstract nature of traditional teaching, all of which impede students' knowledge acquisition.
Objective: This study aims to introduce a novel experimental teaching methodology for severe pelvic trauma, integrating virtual reality (VR) technology as a potent adjunct to existing teaching practices.
Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei.
Nat Commun
January 2025
University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, United Kingdom.
The Trypanosoma brucei genome is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, hundreds of sub-megabase chromosomes contain 177 bp repeats of unknown function, and VSG transcription sites localise to many telomeres.
View Article and Find Full Text PDFThe hidden weavers: A review of DNA/RNA R-loops in stem cell biology and therapeutic potential.
Int J Biol Macromol
January 2025
Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, Guangdong, China. Electronic address:
R-loops, three-stranded nucleic acid structures composed of RNA-DNA hybrids, are increasingly recognized as central regulators of genomic stability and transcription. These structures play critical roles across various cellular processes, including DNA replication, repair, and gene regulation, with significant implications for stem cell biology and disease pathogenesis. This review comprehensively explores the molecular underpinnings of R-loop formation, emphasizing the dual nature of R-loops in both facilitating normal cellular functions and contributing to genomic instability.
View Article and Find Full Text PDFSynergistic protection of nascent DNA at stalled forks by MSANTD4 and BRCA1/2-RAD51.
Nat 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.
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