The access to DNA within nucleosomes is greatly restricted for most enzymes and trans-acting factors that bind DNA. We report here that human DNA ligase I, which carries out the final step of Okazaki fragment processing and of many DNA repair pathways, can access DNA that is wrapped about the surface of a nucleosome in vitro and carry out its enzymatic function with high efficiency. In addition, we find that ligase activity is not affected by the binding of linker histone (H1) but is greatly influenced by the disposition of the core histone tail domains. These results suggest that the window of opportunity for human DNA ligase I may extend well beyond the first stages of chromatin reassembly after DNA replication or repair.
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http://dx.doi.org/10.1093/emboj/19.20.5492 | DOI Listing |
Stem Cell Rev Rep
January 2025
Dipartimento di Medicina Sperimentale, Università di Genova, Viale Benedetto XV, 3, Genova, 16132, Italy.
Progress of human brain in vitro models stands as a keystone in neurological and psychiatric research, addressing the limitations posed by species-specific differences in animal models. The generation of human neurons from induced pluripotent stem cells (iPSCs) using transcription factor reprogramming protocols has been shown to reduce heterogeneity and improve consistency across different stem cell lines. Despite notable advancements, the current protocols still exhibit several shortcomings.
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Histocompatibility and Immunogenetics Laboratory, St. Paul's Hospital, Saskatoon, Saskatchewan, Canada.
The novel allele HLA-C*01:282 has a single non-synonymous mutation compared to HLA- C*01:02:01:01 in codon 100 in Exon 3.
View Article and Find Full Text PDFClin Transl Med
February 2025
Department of Pulmonary and Critical Care Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Background: Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease driven by both environmental and genetic factors. Epigenetics refers to changes in gene expression or cellular phenotype that do not involve alterations to DNA sequence. KMT2A is a member of the SET family which catalyses H3K4 methylation.
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January 2025
Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA.
Mucoepidermoid carcinoma (MEC) is a subtype of epithelial neoplasms commonly found in salivary glands, but can also be seen in the thymus. Diagnosing MEC of the thymus is sometimes challenging due to its histological similarities with adenosquamous carcinoma (ASC). This case report describes a 64-year-old female with a history of metastatic endometrial adenocarcinoma who presented to an oncology clinic with a thymic mass as well as multiple mass lesions in the liver, bone, and abdominal wall.
View Article and Find Full Text PDFAging Cell
January 2025
Hurdle.Bio/Chronomics Ltd., London, UK.
Accessible and non-invasive biomarkers that measure human ageing processes and the risk of developing age-related disease are paramount in preventative healthcare. Here, we describe a novel framework to train saliva-based DNA methylation (DNAm) biomarkers that are reproducible and biologically interpretable. By leveraging a reliability dataset with replicates across tissues, we demonstrate that it is possible to transfer knowledge from blood DNAm to saliva DNAm data using DNAm proxies of blood proteins (EpiScores).
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