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Synergistic 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.
View Article and Find Full Text PDFMolecule interacting with CasL-2 enhances tumor progression and alters radiosensitivity in cervical cancer.
J Transl Med
January 2025
Department of Radiation Oncology, The Second Affiliated Hospital of Dalian Medical University, No. 467 of Zhongshan Road, Shahekou District, Dalian, 116023, China.
Objective: Cervical cancer is a common malignancy among women, and radiotherapy remains a primary treatment modality across all disease stages. However, resistance to radiotherapy frequently results in treatment failure, highlighting the need to identify novel therapeutic targets to improve clinical outcomes.
Methods: The expression of molecule interacting with CasL-2 (MICAL2) was confirmed in cervical cancer tissues and cell lines through western blotting (WB) and immunohistochemistry (IHC).
SRPKs Homolog Dsk1 Regulates Homologous Recombination Repair in Schizosaccharomyces pombe.
Genes Cells
January 2025
Jiangsu Key Laboratory for Pathogens and Ecosystems, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Serine-arginine protein kinases (SRPKs) play important roles in diverse biological processes such as alternative splicing and cell cycle. However, the functions of SRPKs in DNA damage response remain unclear. Here we characterized the function of SRPKs homolog Dsk1 in regulating DNA repair in the fission yeast Schizosaccharomyces pombe.
View Article and Find Full Text PDFTranscriptional analysis reveals the suppression of RAD51 and disruption of the homologous recombination pathway during PEDV infection in IPEC-J2 cells.
Virol J
December 2024
Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China.
PEDV is a highly contagious enteric pathogen that can cause severe diarrhea and death in neonatal pigs. Despite extensive research, the molecular mechanisms of host's response to PEDV infection remain unclear. In this study, differentially expressed genes (DEGs), time-specific coexpression modules, and key regulatory genes associated with PEDV infection were identified.
View Article and Find Full Text PDFThe human RAD52 complex undergoes phase separation and facilitates bundling and end-to-end tethering of RAD51 presynaptic filaments.
bioRxiv
December 2024
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Human RAD52 is a prime target for synthetical lethality approaches to treat cancers with deficiency in homologous recombination. Among multiple cellular roles of RAD52, its functions in homologous recombination repair and protection of stalled replication forks appear to substitute those of the tumor suppressor protein BRCA2. However, the mechanistic details of how RAD52 can substitute BRCA2 functions are only beginning to emerge.
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