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The LIM-domain-only protein LMO2 and its binding partner LDB1 are differentially required for class switch recombination.
Proc Natl Acad Sci U S A
January 2025
Department of Immunology and Microbiology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510000, China.
The LIM-domain-only protein LMO2 interacts with LDB1 in context-dependent multiprotein complexes and plays key roles in erythropoiesis and T cell leukemogenesis, but whether they have any roles in B cells is unclear. Through a CRISPR/Cas9-based loss-of-function screening, we identified LMO2 and LDB1 as factors for class switch recombination (CSR) in murine B cells. LMO2 contributes to CSR at least in part by promoting end joining of DNA double-strand breaks (DSBs) and inhibiting end resection.
View Article and Find Full Text PDFTousled-like kinase loss confers PARP inhibitor resistance in BRCA1-mutated cancers by impeding non-homologous end joining repair.
Mol Med
January 2025
Research Institute, National Cancer Center, Goyang-Si, Gyeonggi-Do, 10408, Republic of Korea.
Background: Double-strand breaks (DSBs) are primarily repaired through non-homologous end joining (NHEJ) and homologous recombination (HR). Given that DSBs are highly cytotoxic, PARP inhibitors (PARPi), a prominent class of anticancer drugs, are designed to target tumors with HR deficiency (HRD), such as those harboring BRCA mutations. However, many tumor cells acquire resistance to PARPi, often by restoring HR in HRD cells through the inactivation of NHEJ.
View Article and Find Full Text PDFOptimizing genome editing efficiency in via a CRISPR/Cas9n-mediated editing system.
Appl Environ Microbiol
January 2025
State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan, China.
is an important bioresource to produce various antibacterial natural products, however, the time-consuming and labor-intensive genome editing toolkits hindered the construction and application of engineered strains, and this study aimed to establish an efficient CRISPR/Cas9n genome editing system in . Initially, the CRISPR/Cas9-mediated editing tool was employed to replace those awkward genome editing tools that relied on homologous recombination, while the off-target Cas9 exhibited high toxicity to Sf01. Therefore, the nickase mutation D10A, high-fidelity mutations including N497A, R661A, Q695A, and Q926A, and thiostrepton-induced promotor P were incorporated into the Cas9 expression cassette, which reduced its toxicity.
View Article and Find Full Text PDFNucleic acid joining enzymes: biological functions and synthetic applications beyond DNA.
Biochem J
January 2025
School of Science, University of Waikato, Hamilton, Waikato, 3216, New Zealand.
DNA-joining by ligase and polymerase enzymes has provided the foundational tools for generating recombinant DNA and enabled the assembly of gene and genome-sized synthetic products. Xenobiotic nucleic acid (XNA) analogues of DNA and RNA with alternatives to the canonical bases, so-called 'unnatural' nucleobase pairs (UBP-XNAs), represent the next frontier of nucleic acid technologies, with applications as novel therapeutics and in engineering semi-synthetic biological organisms. To realise the full potential of UBP-XNAs, researchers require a suite of compatible enzymes for processing nucleic acids on a par with those already available for manipulating canonical DNA.
View Article and Find Full Text PDFExpanding the genomic diversity of human anelloviruses.
Virus Evol
January 2025
MRC-University of Glasgow Centre for Virus Research, The University of Glasgow, Glasgow G61 1QH, United Kingdom.
Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across mammalian hosts. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus genera: , and , while we also present new genomes of the under-sampled , and genera.
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