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| http://dx.doi.org/10.4103/0019-5154.152593 | DOI Listing |
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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 PDFFunctions of the Bloom Syndrome Helicase N-terminal Intrinsically Disordered Region.
Genetics
January 2025
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Bloom Syndrome helicase (Blm) is a RecQ family helicase involved in DNA repair, cell-cycle progression, and development. Pathogenic variants in human BLM cause the autosomal recessive disorder Bloom Syndrome, characterized by predisposition to numerous types of cancer. Prior studies of Drosophila Blm mutants lacking helicase activity or protein have shown sensitivity to DNA damaging agents, defects in repairing DNA double-strand breaks (DSBs), female sterility, and improper segregation of chromosomes in meiosis.
View Article and Find Full Text PDFImpact of social determinants of health on the outcomes of Latin American children with Multisystem Inflammatory Syndrome (MIS-C).
Pediatr Pulmonol
January 2025
Department of Pediatrics & Kawasaki Disease Research Center, University of California San Diego (UCSD) & Rady Children's Hospital, San Diego, California, USA.
Importance: There is growing understanding that Social Determinants of Health (SDH) impact on the outcomes of different pediatric conditions. We aimed to determine whether SDH affect the severity of MIS-C.
Design: Retrospective cohort study, 2021-2023.
The impact of APOE4 on neurological symptoms after exposure to K. brevis neurotoxin.
Environ Toxicol Pharmacol
January 2025
Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA; James A. Haley VA Hospital, Tampa, FL, USA.
Introduction: The harmful alga Karenia brevis (K. brevis) releases brevetoxins (PbTx) that cause respiratory and neurological symptoms. The apolipoprotein E (APOE) ε4 allele has been linked to poor neurological outcomes after exposure to environmental toxicants.
View Article and Find Full Text PDFSingle-Molecule Visualization of BLM-DNA2-Mediated DNA End Resection Using DNA Curtains.
Methods 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.
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