TAR DNA-binding domain protein 43 （TDP-43） is a highly conserved and widely expressed nuclear protein. Nowadays, the expression of TDP-43 can be found in most neurodegenerative diseases such as Alzheimer's disease, which makes it become a neurodegenerative disease associated marker protein. From the current research status at homeland and abroad, and around the relationship between the expression of TDP-43 and brain injury, this article emphatically probes into the specific expression and function of TDP-43 in acute and chronic brain injury based on the knowledge of its biological characteristics, which aims to explore the feasibility for determining the cause of death and the injury and disability situations by TDP-43 in forensic pathology.
Brain Injuries/pathology* ; DNA ; DNA-Binding Proteins/metabolism* ; Humans

Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA. Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors (Canela et al., 2017). Among the various forms of DNA damage, DNA double-strand breaks (DSBs) are particularly harmful. Two major pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are primarily responsible for repairing DSBs (Katsuki et al., 2020; Li and Yuan, 2021; Zhang and Gong, 2021; Xiang et al., 2023). NHEJ is an error-prone repair mechanism that simply joins the broken ends together (Blunt et al., 1995; Hartley et al., 1995). In contrast, HR is a precise repair process. It involves multiple proteins in eukaryotic cells, with the RAD51 recombinase being the key player, which is analogous to bacterial recombinase A (RecA) (Shinohara et al., 1992). The central event in HR is the formation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments that facilitate homology search and DNA strand invasion, ultimately leading to the initiation of repair synthesis (Miné et al., 2007; Hilario et al., 2009; Ma et al., 2017).
Recombinational DNA Repair ; DNA-Binding Proteins/metabolism* ; DNA Repair ; DNA Damage ; DNA

The genomic instability may lead to an initiation of cancer in many organisms. Homologous recombination repair (HRR) is vital in maintaining cellular genomic stability. RAD51 associated protein 1 (RAD51AP1), which plays a crucial role in HRR and primarily participates in forming D-loop, was reported as an essential protein for maintaining cellular genomic stability. However, recent studies showed that RAD51AP1 was significantly overexpressed in various cancer types and correlated with poor prognosis. These results suggested that RAD51AP1 may play a significant pro-cancer effect in multiple cancers. The underlying mechanism is still unclear. Cancer stemness-maintaining effects of RAD51AP1 might be considered as the most reliable mechanism. Meanwhile, RAD51AP1 also promoted resistance to radiation therapy and chemotherapy in many cancers. Thus, researches focused on RAD51AP1, and its regulatory molecules may provide new targets for overcoming cancer progression and treatment resistance. Here, we reviewed the latest research on RAD51AP1 in cancers and summarized its differential expression and prognostic implications. In this review, we also outlined the potential mechanisms of its pro-cancer and drug resistance-promoting effects to provide several potential directions for further research.
.
Humans ; DNA-Binding Proteins/metabolism* ; RNA-Binding Proteins/metabolism* ; Lung Neoplasms ; DNA Repair ; Genomic Instability ; Rad51 Recombinase/metabolism*

DNA methylation is a significant epigenetic modification mode, which plays an important role in embryo reprogramming, stem cell differentiation and tumor occurrence. The ten-eleven translocation (TET) enzyme is a crucial demethylation enzyme, which can catalyze 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine(5caC). These bases represent the epigenetic modifications of DNA and regulate the process of DNA methylation. Understanding the role of TET enzyme in regulating the DNA methylation modification and gene expression can help us to gain the knowledge for the normal growth development and epigenetic regulation in human diseases.
5-Methylcytosine ; metabolism ; Cell Differentiation ; DNA ; DNA Methylation ; DNA-Binding Proteins ; Epigenesis, Genetic ; Humans

Ingestion of food affects secretion of hormones from enteroendocrine cells located in the gastrointestinal mucosa. These hormones are involved in the regulation of various gastrointestinal functions including the control of food intake. One cell in the stomach, the X/A-like has received much attention over the past years due to the production of ghrelin. Until now, ghrelin is the only known orexigenic hormone that is peripherally produced and centrally acting to stimulate food intake. Subsequently, additional peptide products of this cell have been described including desacyl ghrelin, obestatin and nesfatin-1. Desacyl ghrelin seems to be involved in the regulation of food intake as well and could play a counter-balancing role of ghrelin's orexigenic effect. In contrast, the initially proposed anorexigenic action of obestatin did not hold true and therefore the involvement of this peptide in the regulation of feeding is questionable. Lastly, the identification of nesfatin-1 in the same cell in different vesicles than ghrelin extended the function of this cell type to the inhibition of feeding. Therefore, this X/A-like cell could play a unique role by encompassing yin and yang properties to mediate not only hunger but also satiety.
Calcium-Binding Proteins ; DNA-Binding Proteins ; Eating ; Enteroendocrine Cells ; Ghrelin ; Hunger ; Mucous Membrane ; Nerve Tissue Proteins ; Obesity ; Stomach

Cloning, Molecular ; DNA ; genetics ; DNA-Binding Proteins ; genetics ; Humans ; Proteins ; genetics ; Sequence Analysis, DNA ; Two-Hybrid System Techniques ; Yeasts ; genetics

This study was aimed to explore the pathogenesis of type III familial hemophagocytic lymphohistiocytosis (FHL3) via susceptibility gene UNC13D involving in homologous recombination repair (HRR) of DNA double-strand break (DSB). By means of DNA homologous recombination repair, the change of homologous recombination repair rate of normal control cells and DR-U2OS cells after down-regulation of UNC13D was detected; the UNC13D gene related function was explored. The results showed that DR-U2OS cells displayed a significant reduction in homologous recombination repair of DNA DSB after siRNA knockdown of UNC13D, compared to its normal control cell counterparts (P < 0.05), suggesting that UNC13D was involved in DNA double-stranded breakage repair. It is concluded that UNC13D gene mutation may be involved in the pathogenesis of FHL3 via its dual effects of both the cytotoxic granule exocytosis and decrease of homologous recombination repair rate after the DNA double-strand break, therefore, providing a new theoretical basis to reveal the pathogenesis of FHL3.
DNA Breaks, Double-Stranded ; DNA-Binding Proteins ; genetics ; Humans ; Lymphohistiocytosis, Hemophagocytic ; classification ; genetics ; Membrane Proteins ; genetics ; Recombinational DNA Repair

Animals ; Antigens, Nuclear ; DNA ; genetics ; metabolism ; DNA Breaks, Double-Stranded ; DNA Repair ; DNA-Binding Proteins ; Humans ; Ku Autoantigen

OBJECTIVE: To analyze the dynamic molecular expression characteristics of single cell RNA binding proteins (RBPs) in the development of mouse embryonic hematopoitic stem cells (HSCs), and obtain the functional research target RNA splicing factor--Mbnl1, to clarify the function of Mbnl1 involved in regulating mouse embryonic HSC development. METHODS: Bioinformatics was used to analyze the single-cell transcriptome data of mouse embryos during HSC development, and the single-cell RBP dynamic molecular expression maps in HSC development was obtained. Mbnl1 was obtained by combining differential analysis and literature research screening. The Mbnl1-knockout mouse model was constructed by the CRISPER/Cas9 technology. Aorta-gonad-mesonephros (AGM) and yolk sac (YS) tissue in two genotype embryos of Mbnl1 RESULTS: The in vitro CFU-C experiment of hematopoietic cells preliminarily indicated that there was no significant difference in the number of cell colonies in AGM region and YS transformed by the two genotypes of Mbnl1 CONCLUSION Through functional experiments in vivo and in vitro, it has been confirmed that knockout of the RNA splicing factor--Mbnl1 does not affect the development of HSPC in AGM region of mouse embryo.
Animals ; DNA-Binding Proteins ; Gonads ; Hematopoiesis ; Hematopoietic Stem Cells ; Mesonephros ; Mice ; RNA-Binding Proteins/genetics* ; Yolk Sac

OBJECTIVETo clarify the regulatory elements of Rad51 gene in its 5'flanking region.

METHODSVarious constructs were obtained by cloning different DNA fragments into pGL3 reporter vector. These constructs were then introduced into osteosarcoma cell line U2-OS by calcium phosphate method for transient expression of reporter gene, and luciferase activities were measured by luciferase assay.

RESULTSCells transfected with pGL3 constructs containing fragment -964 to +1430 and -733 to +1430 showed high luciferase activities. Obvious elevation of luciferase activities was also observed in cells transfected with pGL3 constructs containing four shorter derivative fragments -964 to -412, -746 to -412, -651 to -412 and -536 to -412. The highest luciferase activities were measured in transfected cells with plasmids containing fragment -964 to -412, and the lowest were in transfected cells with plasmids containing fragment -536 to -412. Luciferase activities in transfected cells with plasmids containing fragment -651 to -412 were higher than that in transfected cells with plasmids containing fragment -746 to -412.

CONCLUSIONIt is believable that the basic transcription-promoting element (promoter) for Rad51 gene resides between -536 to -412, and two transcription-enhancing elements (enhancer) or binding sites of positive transcription factors reside between -651 to -536 and -964 to -746, whereas one transcription-inhibiting element (silencer) or binding site of negative transcription factor may reside between -746 to -651.