Genes to Cells最新文献_第5页

Elimination of physiological senescent cutaneous cells in a novel p16-dependent senolytic mouse model impacts lipid metabolism in skin aging 在新型 p16 依赖性衰老小鼠模型中消除生理性衰老皮肤细胞会影响皮肤老化过程中的脂质代谢

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-16 DOI: 10.1111/gtc.13163

Yuma Sugiyama, Yoichiro Kawabe, Tanenobu Harada, Yu Aoki, Keiko Tsuji, Daijiro Sugiyama, Mitsuo Maruyama

{"title":"Elimination of physiological senescent cutaneous cells in a novel p16-dependent senolytic mouse model impacts lipid metabolism in skin aging","authors":"Yuma Sugiyama, Yoichiro Kawabe, Tanenobu Harada, Yu Aoki, Keiko Tsuji, Daijiro Sugiyama, Mitsuo Maruyama","doi":"10.1111/gtc.13163","DOIUrl":"10.1111/gtc.13163","url":null,"abstract":"The evidence of the correlation between cellular senescence and aging has increased in research with animal models. These models have been intentionally generated to target and regulate cellular senescent cells with the promoter activity of p16Ink4a or p19Arf, genes that are highly expressed in aging cells. However, the senolytic efficiency in various organs and cells from these models represents unexpected variation and diversity in some cases. We have generated a novel knock-in model, p16tdT-hDTR mice, which possess tdTomato and human diphtheria toxin receptor (hDTR) downstream of Cdkn2a, an endogenous p16Ink4a gene. We successfully demonstrated that p16-derived tdTomato and hDTR expressions are observed in these mouse embryo fibroblasts and following treatment with diphtheria toxin (DT) eliminates those cells. Furthermore, we demonstrated the efficacy of eliminating p16-positive cells in vivo, and also observed a tendency to decrease their cutaneous SA-β-gal activity after subcutaneous DT injection into p16tdT-hDTR mice. In particular, comprehensive gene expression analysis in skin revealed that upregulated genes related to lipid metabolisms with aging exhibited remarkable expressions under the senolysis. These results clearly unveiled p16-positive senescent cells contribute to age-related changes in skin.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"1085-1094"},"PeriodicalIF":1.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accelerated BDNF expression in visceral white adipose tissues following high-fat diet feeding in mice 小鼠摄入高脂饮食后，内脏白色脂肪组织中 BDNF 的表达加速。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-15 DOI: 10.1111/gtc.13162

Kurumi Sakata, Mamoru Fukuchi

{"title":"Accelerated BDNF expression in visceral white adipose tissues following high-fat diet feeding in mice","authors":"Kurumi Sakata, Mamoru Fukuchi","doi":"10.1111/gtc.13162","DOIUrl":"10.1111/gtc.13162","url":null,"abstract":"Brain-derived neurotrophic factor (BDNF) is expressed in the white adipose tissues (WATs), and the expression increases during high-fat diet (HFD) feeding, implicating its role in obesity. Here, we focused on BDNF expression in epididymal WAT (eWAT), a visceral adipose tissue, in mice. During 2 weeks of HFD feeding, Bdnf mRNA expression in eWAT slightly increased, but a robust increase was observed after 8 weeks of HFD feeding. This upregulation of Bdnf mRNA was correlated with significant induction of hypoxia-inducible factor 1α (Hif1α) and platelet-derived growth factor subunit B (Pdgfb) mRNA in eWAT following 8 weeks of HFD feeding. Furthermore, the increased expression of the M1 macrophage markers was strongly correlated with the elevation of Bdnf mRNA in the eWAT. Notably, 8 weeks of HFD feeding significantly elevated Tnfα mRNA expression in eWAT, while no such induction was observed in inguinal WAT (iWAT). In contrast, the expression of Adipoq (adiponectin), implicated in improved insulin sensitivity and anti-inflammatory effects, was significantly upregulated in iWAT, but not in eWAT. Thus, our study may show the role of BDNF in eWAT in obesity models, potentially contributing to the pathological state of visceral adipose tissues.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"1077-1084"},"PeriodicalIF":1.3,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neonatal Fc receptor is a functional receptor for classical human astrovirus 新生儿 Fc 受体是经典人类星状病毒的功能性受体

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-12 DOI: 10.1111/gtc.13160

Kei Haga, Takashi Tokui, Kana Miyamoto, Reiko Takai-Todaka, Shiori Kudo, Azusa Ishikawa, Ryoka Ishiyama, Akiko Kato, Masaru Yokoyama, Kazuhiko Katayama, Akira Nakanishi

{"title":"Neonatal Fc receptor is a functional receptor for classical human astrovirus","authors":"Kei Haga, Takashi Tokui, Kana Miyamoto, Reiko Takai-Todaka, Shiori Kudo, Azusa Ishikawa, Ryoka Ishiyama, Akiko Kato, Masaru Yokoyama, Kazuhiko Katayama, Akira Nakanishi","doi":"10.1111/gtc.13160","DOIUrl":"10.1111/gtc.13160","url":null,"abstract":"Human astrovirus (HAstV) is a global cause of gastroenteritis in infants, the elderly, and the immunocompromised. However, the molecular mechanisms that control its susceptibility are not fully understood, as the functional receptor used by the virus has yet to be identified. Here, a genome-wide CRISPR-Cas9 library screen in Caco2 cells revealed that the neonatal Fc receptor (FcRn) can function as a receptor for classical HAstV (Mamastrovirus genotype 1). Deletion of FCGRT or B2M, which encode subunits of FcRn, rendered Caco2 cells and intestinal organoid cells resistant to HAstV infection. We also showed that human FcRn expression renders non-susceptible cells permissive to viral infection and that FcRn binds directly to the HAstV spike protein. Therefore, our findings provide insight into the entry mechanism of HAstV into susceptible cells. We anticipate that this information can be used to develop new therapies targeting human astroviruses, providing new strategies to treat this global health issue.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"983-1001"},"PeriodicalIF":1.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Capsaicin modulates TRPV1, induces β-defensin expression, and regulates NF-κB in oral senescent cells and a murine model 辣椒素在口腔衰老细胞和小鼠模型中调节 TRPV1、诱导β-防御素表达并调节 NF-κB

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-12 DOI: 10.1111/gtc.13158

Yoriko Ikuyo, Haruna Yokoi, Jingshu Wang, Masae Furukawa, Resmi Raju, Mitsuyoshi Yamada, Yu Aoki, Kenji Matsushita

{"title":"Capsaicin modulates TRPV1, induces β-defensin expression, and regulates NF-κB in oral senescent cells and a murine model","authors":"Yoriko Ikuyo, Haruna Yokoi, Jingshu Wang, Masae Furukawa, Resmi Raju, Mitsuyoshi Yamada, Yu Aoki, Kenji Matsushita","doi":"10.1111/gtc.13158","DOIUrl":"10.1111/gtc.13158","url":null,"abstract":"Aging is associated with a decline in oral immune function, marked by reduced levels of antimicrobial peptides such as defensins. Capsaicin, a bioactive component found in chili peppers, has been theorized to modulate immune responses through specific receptor pathways. This study examined the effects of aging on oral defensin levels and the potential mitigating role of capsaicin, mediated by the immune response in oral tissues. We conducted a comparative analysis between young and aged mice, with or without capsaicin supplementation, for 3 months. The effect of capsaicin was also studied in vitro in senescence-induced human oral keratinocytes. We found that aging did not reduce defensin levels uniformly but did so in some instances. Capsaicin treatment increased defensin levels in these cases, potentially through transient receptor potential cation channel subfamily V member 1 (TRPV1)-mediated pathways in the oral cavity. Capsaicin supplementation may counteract age-related declines in oral defensin levels, enabling the maintenance of oral immune function during aging.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"1069-1076"},"PeriodicalIF":1.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of luminescent probes for real-time detection of the CDK/PP2A balance during the cell cycle 开发用于实时检测细胞周期中 CDK/PP2A 平衡的发光探针

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-11 DOI: 10.1111/gtc.13159

Hirotsugu Hino, Kaori Takaki, Mika Kobe, Satoru Mochida

{"title":"Development of luminescent probes for real-time detection of the CDK/PP2A balance during the cell cycle","authors":"Hirotsugu Hino, Kaori Takaki, Mika Kobe, Satoru Mochida","doi":"10.1111/gtc.13159","DOIUrl":"10.1111/gtc.13159","url":null,"abstract":"From a biochemical viewpoint, the cell cycle is controlled by the phosphorylation of cyclin-dependent kinase (CDK) substrates, and the phosphorylation level is determined by the enzymatic balance between CDK and protein phosphatase 2A (PP2A). However, the conventional techniques for analyzing protein phosphorylation using radioisotopes and antibodies involve many operational steps and take days before obtaining results, making them difficult to apply to high-throughput screening and real-time observations. In this study, we developed luminescent probes with a light intensity that changes depending on its phosphorylation state. We modified the Nano-lantern probe (Renilla luciferase-based Ca2+ probe) by introducing a CDK-substrate peptide and a phosphopeptide-binding domain into the luciferase. Our initial trial resulted in new probes that could report the CDK/PP2A balance in a purified system. Further modifications of these probes (replacing the phospho-Ser with phospho-Thr and randomly replacing its surrounding amino acids) improved the dynamic range by up to four-fold, making them practical for use in the Xenopus egg extracts system, where many physiological events can be reproduced. Taken together, our new probes enabled the monitoring of the CDK/PP2A balance in real time, and are applicable to high-throughput systems; the new probes thus appear promising for use in substrate and drug screening.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"1002-1011"},"PeriodicalIF":1.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA–DNA hybrids on protein coding genes are stabilized by loss of RNase H and are associated with DNA damages during S-phase in fission yeast 蛋白质编码基因上的 RNA-DNA 杂交因 RNase H 的缺失而稳定，并与裂殖酵母 S 期的 DNA 损伤有关

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-09 DOI: 10.1111/gtc.13157

Tomoko Sagi, Daichi Sadato, Kazuto Takayasu, Hiroyuki Sasanuma, Yutaka Kanoh, Hisao Masai

{"title":"RNA–DNA hybrids on protein coding genes are stabilized by loss of RNase H and are associated with DNA damages during S-phase in fission yeast","authors":"Tomoko Sagi, Daichi Sadato, Kazuto Takayasu, Hiroyuki Sasanuma, Yutaka Kanoh, Hisao Masai","doi":"10.1111/gtc.13157","DOIUrl":"10.1111/gtc.13157","url":null,"abstract":"RNA–DNA hybrid is a part of the R-loop which is an important non-standard nucleic acid structure. RNA–DNA hybrid/R-loop causes genomic instability by inducing DNA damages or inhibiting DNA replication. It also plays biologically important roles in regulation of transcription, replication, recombination and repair. Here, we have employed catalytically inactive human RNase H1 mutant (D145N) to visualize RNA–DNA hybrids and map their genomic locations in fission yeast cells. The RNA–DNA hybrids appear as multiple nuclear foci in rnh1∆rnh201∆ cells lacking cellular RNase H activity, but not in the wild-type. The majority of RNA–DNA hybrid loci are detected at the protein coding regions and tRNA. In rnh1∆rnh201∆ cells, cells with multiple Rad52 foci increase during S-phase and about 20% of the RNA–DNA hybrids overlap with Rad52 loci. During S-phase, more robust association of Rad52 with RNA–DNA hybrids was observed in the protein coding region than in M-phase. These results suggest that persistent RNA–DNA hybrids in the protein coding region in rnh1∆rnh201∆ cells generate DNA damages during S-phase, potentially through collision with DNA replication forks.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"966-982"},"PeriodicalIF":1.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dose-dependent effects of histone methyltransferase NSD2 on site-specific double-strand break repair 组蛋白甲基转移酶 NSD2 对位点特异性双链断裂修复的剂量依赖性效应

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-08 DOI: 10.1111/gtc.13156

Koh Iwasaki, Akari Tojo, Haruka Kobayashi, Kai Shimizu, Yoshitaka Kamimura, Yasunori Horikoshi, Atsuhiko Fukuto, Jiying Sun, Manabu Yasui, Masamitsu Honma, Atsushi Okabe, Ryoji Fujiki, Nakako Izumi Nakajima, Atsushi Kaneda, Satoshi Tashiro, Akira Sassa, Kiyoe Ura

{"title":"Dose-dependent effects of histone methyltransferase NSD2 on site-specific double-strand break repair","authors":"Koh Iwasaki, Akari Tojo, Haruka Kobayashi, Kai Shimizu, Yoshitaka Kamimura, Yasunori Horikoshi, Atsuhiko Fukuto, Jiying Sun, Manabu Yasui, Masamitsu Honma, Atsushi Okabe, Ryoji Fujiki, Nakako Izumi Nakajima, Atsushi Kaneda, Satoshi Tashiro, Akira Sassa, Kiyoe Ura","doi":"10.1111/gtc.13156","DOIUrl":"10.1111/gtc.13156","url":null,"abstract":"Histone modifications are catalyzed and recognized by specific proteins to regulate dynamic DNA metabolism processes. NSD2 is a histone H3 lysine 36 (H3K36)-specific methyltransferase that is associated with both various transcription regulators and DNA repair factors. Specifically, it has been implicated in the repair of DNA double-strand breaks (DSBs); however, the role of NSD2 during DSB repair remains enigmatic. Here, we show that NSD2 does not accumulate at DSB sites and that it is not further mobilized by DSB formation. Using three different DSB repair reporter systems, which contained the endonuclease site in the active thymidine kinase gene (TK) locus, we demonstrated separate dose-dependent effects of NSD2 on homologous recombination (HR), canonical-non-homologous end joining (c-NHEJ), and non-canonical-NHEJ (non-c-NHEJ). Endogenous NSD2 has a role in repressing non-c-NHEJ, without affecting DSB repair efficiency by HR or total NHEJ. Furthermore, overexpression of NSD2 promotes c-NHEJ repair and suppresses HR repair. Therefore, we propose that NSD2 has functions in chromatin integrity at the active regions during DSB repair.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"951-965"},"PeriodicalIF":1.3,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of genes contributing to attenuation of rat model of galactose-induced cataract by pyruvate 鉴定有助于减轻丙酮酸葡萄糖诱发白内障大鼠模型的基因。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-01 DOI: 10.1111/gtc.13150

Fuuga Masuda, Mayumi Inami, Yoshihiro Takamura, Masaru Inatani, Masaya Oki

{"title":"Identification of genes contributing to attenuation of rat model of galactose-induced cataract by pyruvate","authors":"Fuuga Masuda, Mayumi Inami, Yoshihiro Takamura, Masaru Inatani, Masaya Oki","doi":"10.1111/gtc.13150","DOIUrl":"10.1111/gtc.13150","url":null,"abstract":"Cataracts are a disease that reduces vision due to opacity formation of the lens. Diabetic cataracts occur at young age and progress relatively quickly, so the development of effective treatment has been awaited. Several studies have shown that pyruvate inhibits oxidative stress and glycation of lens proteins, which contribute to onset of diabetic cataracts. However, detailed molecular mechanisms have not been revealed. In this study, we attempted to reduce galactose-induced opacity by pyruvate with rat ex vivo model. Rat lenses were extracted and cultured in galactose-containing medium to induce lens opacity. After opacity had developed, continued culturing with pyruvate in the medium resulted in a reduction of lens opacity. Subsequently, we conducted microarray analysis to investigate the genes that contribute to the therapeutic effect. We performed quantitative expression measurements using RT-qPCR for extracted genes that were upregulated in cataract-induced lenses and downregulated in pyruvate-treated lenses, resulting in the identification of 34 candidate genes. Functional analysis using the STRING database suggests that metallothionein-related factors (Mt1a, Mt1m, and Mt2A) and epithelial-mesenchymal transition-related factors (Acta2, Anxa1, Cd81, Mki67, Timp1, and Tyms) contribute to the therapeutic effect of cataracts.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 10","pages":"876-888"},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

L3MBTL2 maintains MYCN-amplified neuroblastoma cell proliferation through silencing NRIP3 and BRME1 genes L3MBTL2 通过沉默 NRIP3 和 BRME1 基因维持 MYCN 扩增的神经母细胞瘤细胞增殖。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-08-27 DOI: 10.1111/gtc.13148

Ryu Okada, Hisanori Takenobu, Shunpei Satoh, Ryuichi P. Sugino, Ritsuko Onuki, Masayuki Haruta, Kyosuke Mukae, Atsuko Nakazawa, Jesmin Akter, Miki Ohira, Takehiko Kamijo

{"title":"L3MBTL2 maintains MYCN-amplified neuroblastoma cell proliferation through silencing NRIP3 and BRME1 genes","authors":"Ryu Okada, Hisanori Takenobu, Shunpei Satoh, Ryuichi P. Sugino, Ritsuko Onuki, Masayuki Haruta, Kyosuke Mukae, Atsuko Nakazawa, Jesmin Akter, Miki Ohira, Takehiko Kamijo","doi":"10.1111/gtc.13148","DOIUrl":"10.1111/gtc.13148","url":null,"abstract":"Epigenetic alterations critically affect tumor development. Polycomb-group complexes constitute an evolutionarily conserved epigenetic machinery that regulates stem cell fate and development. They are implicated in tumorigenesis, primarily via histone modification. Polycomb repressive complex 1 (PRC1) complexes 1–6 (PRC1.1–6) mediate the ubiquitination of histone H2A on lysine 119 (H2AK119ub). Here, we studied the functional roles of a PRC1.6 molecule, L3MBTL2, in neuroblastoma (NB) cells. L3MBTL2-knockout and knockdown revealed that L3MBTL2 depletion suppressed NB cell proliferation via cell-cycle arrest and gamma-H2A.X upregulation. L3MBTL2-knockout profoundly suppressed xenograft tumor formation. Transcriptome analysis revealed suppressed cell-cycle-related and activated differentiation-related pathways. Break repair meiotic recombinase recruitment factor 1 (BRME1) and nuclear receptor interacting protein 3 (NRIP3) were notably de-repressed by L3MBTL2-knockout. The deletion of L3MBTL2 reduced enrichment of H2AK119ub and PCGF6 at transcriptional start site proximal regions of the targets. Add-back studies unveiled the importance of L3MBTL2-BRME1 and -NRIP3 axes for NB cell proliferation. We further manifested the association of MYCN with de-repression of NRIP3 in an L3MBTL2-deficient context. Therefore, this study first revealed the significance of L3MBTL2-mediated gene silencing in MYCN-amplified NB cells.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 10","pages":"838-853"},"PeriodicalIF":1.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RAD18- and BRCA1-dependent pathways promote cellular tolerance to the nucleoside analog ganciclovir 依赖于 RAD18 和 BRCA1 的途径可促进细胞对核苷类似物更昔洛韦的耐受性。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-08-22 DOI: 10.1111/gtc.13155

Tasnim Ahmad, Ryotaro Kawasumi, Kouji Hirota

{"title":"RAD18- and BRCA1-dependent pathways promote cellular tolerance to the nucleoside analog ganciclovir","authors":"Tasnim Ahmad, Ryotaro Kawasumi, Kouji Hirota","doi":"10.1111/gtc.13155","DOIUrl":"10.1111/gtc.13155","url":null,"abstract":"Ganciclovir (GCV) is a clinically important drug as it is used to treat viral infections. GCV is incorporated into the DNA during replication, where it interferes with subsequent replication on GCV-incorporated templates. However, the effects of GCV on the host genome and the mechanisms underlying cellular tolerance to GCV remain unclear. In this study, we explored these mechanisms using a collection of mutant DT40 cells. We identified RAD17/−, BRCA1−/−, and RAD18−/− cells as highly GCV-sensitive. RAD17, a component of the alternative checkpoint-clamp loader RAD17-RFC, was required for the activation of the intra-S checkpoint following GCV treatment. BRCA1, a critical factor for promoting homologous recombination (HR), was required for suppressing DNA double-strand breaks (DSBs). Moreover, RAD18, an E3-ligase involved in DNA repair, was critical in suppressing the aberrant ligation of broken chromosomes caused by GCV. We found that BRCA1 suppresses DSBs through HR-mediated repair and template switching (TS)-mediated damage bypass. Moreover, the strong GCV sensitivity of BRCA1−/− cells was rescued by the loss of 53BP1, despite the only partial restoration in the sister chromatid exchange events which are hallmarks of HR. These results indicate that BRCA1 promotes cellular tolerance to GCV through two mechanisms, TS and HR-mediated repair.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"935-950"},"PeriodicalIF":1.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0