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Evaluating the significance of various forms of DNA damage is complicated by discoveries that some lesions inactivate repair enzymes or produce more deleterious forms of damage. Histone lysines within nucleosomes react with the commonly produced C4'-oxidized abasic site (C4-AP) to concomitantly yield an electrophilic modification (K) on lysine and DNA strand scission. We developed a chemoproteomic approach to identify K in HeLa cells. More than 60 000 K-modified histones are produced per cell. Using LC-MS/MS, we detected K at 17 of the 57 lysine residues distributed throughout the four core histone proteins. Therefore, K constitutes a DNA damage-induced, nonenzymatic histone post-translational modification. K formation suggests that downstream processes resulting from DNA damage could have ramifications on cells.
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http://dx.doi.org/10.1021/jacs.2c02880 | DOI Listing |
BMB Rep
September 2025
Department of Molecular Biology, Dankook University, Cheonan 31116, Korea.
Anaphase-promoting complex/cyclosome (APC/C) regulates the cell cycle by destruction of target proteins ubiquitination. However, understanding the control of APC/C has remained elusive. We identify APC2, the catalytic core subunit of APC/C, as a binding partner of active regulator of SIRT1 (AROS).
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
July 2025
Jiangsu Suzhong Pharmaceutical Research Institute Nanjing 210031,China.
This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively.
View Article and Find Full Text PDFTissue Cell
August 2025
Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt. Electronic address:
The present novel trial assesses the prophylactic influence of ZnO NPs in comparison to silymarin against liver damage induced by acetaminophen (APAP). Forty albino rats were allocated into 4 groups (n = `10 rats/ group). Group I (Control), was orally administered 0.
View Article and Find Full Text PDFEMBO J
August 2025
Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, 3015 GD, The Netherlands.
The DNA Damage Response (DDR) is a highly regulated process that safeguards genomic integrity against DNA lesions. Increasing evidence supports a reciprocal relationship between damaged chromatin architecture and the signalling pathways that coordinate the DDR. However, the mechanisms underlying this interplay in response to transcription-blocking DNA lesions remain largely unexplored.
View Article and Find Full Text PDFPLoS One
August 2025
Medical School of Nantong University, Nantong, China.
Caliban, the Drosophila ortholog of human Nuclear export mediator factor (NEMF), is a recently identified regulator of the intrinsic apoptotic signaling pathway in response to DNA damage; however, the mechanism governing its expression after DNA damage remains unclear. In this study, we demonstrated that DNA damage upregulated caliban expression concomitant with p53 activation. Over-expression of p53 upregulated the mRNA and protein levels of caliban.
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