It is generally thought that the DNA-damage checkpoint kinases, ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), work independently of one another. Here, we show that ATM and the nuclease activity of meiotic recombination 11 (Mre11) are required for the processing of DNA double-strand breaks (DSBs) to generate the replication protein A (RPA)-coated ssDNA that is needed for ATR recruitment and the subsequent phosphorylation and activation of Chk1. Moreover, we show that efficient ATM-dependent ATR activation in response to DSBs is restricted to the S and G2 cell cycle phases and requires CDK kinase activity. Thus, in response to DSBs, ATR activation is regulated by ATM in a cell-cycle dependent manner.
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http://dx.doi.org/10.1038/ncb1337 | DOI Listing |
iScience
January 2025
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
The regulation of gene expression relies on the coordinated action of transcription factors (TFs) at enhancers, including both activator and repressor TFs. We employed deep learning (DL) to dissect HepG2 enhancers into positive (PAR), negative (NAR), and neutral activity regions. Sharpr-MPRA and STARR-seq highlight the dichotomy impact of NARs and PARs on modulating and catalyzing the activity of enhancers, respectively.
View Article and Find Full Text PDFJ Inflamm Res
January 2025
Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, 210009, People's Republic of China.
Objective: This study evaluated the diagnostic value of plasma Neutrophil extracellular traps (NETs) levels and the index of cardiac electrophysiological balance (iCEB) in identifying silent myocardial ischemia (SMI) in maintenance hemodialysis (MHD) patients.
Methods: This cross-sectional observational study involved patients receiving MHD treatment. Data were collected on coronary angiography performed in our hospital from February 2023 to February 2024.
Respir Med Case Rep
January 2025
Department of Rheumatology of Lucania - UOSD of Rheumatology, "Madonna delle Grazie" Hospital, Matera, Italy.
Background: Anti-Ku antibodies are autoantibodies directed against the Ku protein complex involved in DNA repair. They are typically associated with overlap syndromes featuring polymyositis and systemic sclerosis. Isolated pulmonary involvement without myositis is exceedingly rare.
View Article and Find Full Text PDFWorld Allergy Organ J
January 2025
Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background: While epidemiological data suggest a connection between atopic dermatitis (AD) and COVID-19, the molecular mechanisms underlying this relationship remain unclear.
Objective: To investigate whether COVID-19-related CpGs may contribute to AD development and whether this association is mediated through the regulation of specific genes' expression.
Methods: We combined Mendelian randomization and transcriptome analysis for data-driven explorations.
Cytotechnology
April 2025
Department of Genetics, Osmania University, Hyderabad, Telangana State India.
Targeting tumor angiogenesis with safe endogenous protein inhibitors is a promising therapeutic approach despite the plethora of the first line of emerging chemotherapeutic drugs. The extracellular matrix network in the blood vessel basement membrane and growth factors released from endothelial and tumor cells promote the neovascularization which supports the tumor growth. Contrastingly, small cleaved cryptic fragments of the C-terminal non collagenous domains of the same basement membrane display antiangiogenic effect.
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