Genes & development最新文献_第5页

Tolerance thresholds underlie responses to DNA damage during germline development. 耐受阈值是生殖细胞发育过程中 DNA 损伤反应的基础。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-08-20 DOI: 10.1101/gad.351701.124

Gloria Jansen, Daniel Gebert, Tharini Ravindra Kumar, Emily Simmons, Sarah Murphy, Felipe Karam Teixeira

{"title":"Tolerance thresholds underlie responses to DNA damage during germline development.","authors":"Gloria Jansen, Daniel Gebert, Tharini Ravindra Kumar, Emily Simmons, Sarah Murphy, Felipe Karam Teixeira","doi":"10.1101/gad.351701.124","DOIUrl":"10.1101/gad.351701.124","url":null,"abstract":"Selfish DNA modules like transposable elements (TEs) are particularly active in the germline, the lineage that passes genetic information across generations. New TE insertions can disrupt genes and impair the functionality and viability of germ cells. However, we found that in P-M hybrid dysgenesis in Drosophila, a sterility syndrome triggered by the P-element DNA transposon, germ cells harbor unexpectedly few new TE insertions despite accumulating DNA double-strand breaks (DSBs) and inducing cell cycle arrest. Using an engineered CRISPR-Cas9 system, we show that generating DSBs at silenced P-elements or other noncoding sequences is sufficient to induce germ cell loss independently of gene disruption. Indeed, we demonstrate that both developing and adult mitotic germ cells are sensitive to DSBs in a dosage-dependent manner. Following the mitotic-to-meiotic transition, however, germ cells become more tolerant to DSBs, completing oogenesis regardless of the accumulated genome damage. Our findings establish DNA damage tolerance thresholds as crucial safeguards of genome integrity during germline development.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"631-654"},"PeriodicalIF":7.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Corrigendum: XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. 更正：神经系统中 XBP-1 的缺乏可通过增加自噬作用防止肌萎缩性脊髓侧索硬化症。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-08-01 DOI: 10.1101/gad.352249.124

Claudio Hetz, Peter Thielen, Soledad Matus, Melissa Nassif, Felipe Court, Roberta Kiffin, Gabriela Martinez, Ana Maria Cuervo, Robert H Brown, Laurie H Glimcher

引用次数: 0

Corrigendum: TAp73 is a central transcriptional regulator of airway multiciliogenesis. 更正：TAp73 是气道多纤毛生成的核心转录调节因子。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-08-01 DOI: 10.1101/gad.352194.124

Alice Nemajerova, Daniela Kramer, Saul S Siller, Christian Herr, Orr Shomroni, Tonatiuh Pena, Cristina Gallinas Suazo, Katharina Glaser, Merit Wildung, Henrik Steffen, Anusha Sriraman, Fabian Oberle, Magdalena Wienken, Magali Hennion, Ramon Vidal, Bettina Royen, Mihai Alevra, Detlev Schild, Robert Bals, Jürgen Dönitz, Dietmar Riedel, Stefan Bonn, Ken-Ichi Takemaru, Ute M Moll, Muriel Lizé

引用次数: 0

Comparing the roles of sex chromosome-encoded protein homologs in gene regulation 比较性染色体编码蛋白同源物在基因调控中的作用

IF 10.5 1区生物学

Genes & development Pub Date : 2024-07-24 DOI: 10.1101/gad.351890.124

Ellen Lavorando, Michael C. Owens, Kathy Fange Liu

引用次数: 0

SUMO promotes DNA repair protein collaboration to support alternative telomere lengthening in the absence of PML 在缺乏 PML 的情况下，SUMO 促进 DNA 修复蛋白的协作，以支持端粒的替代性延长

IF 10.5 1区生物学

Genes & development Pub Date : 2024-07-22 DOI: 10.1101/gad.351667.124

Rongwei Zhao, Meng Xu, Xiaoyang Yu, Anne R. Wondisford, Rachel M. Lackner, Jayme Salsman, Graham Dellaire, David M. Chenoweth, Roderick J. O'Sullivan, Xiaolan Zhao, Huaiying Zhang

{"title":"SUMO promotes DNA repair protein collaboration to support alternative telomere lengthening in the absence of PML","authors":"Rongwei Zhao, Meng Xu, Xiaoyang Yu, Anne R. Wondisford, Rachel M. Lackner, Jayme Salsman, Graham Dellaire, David M. Chenoweth, Roderick J. O'Sullivan, Xiaolan Zhao, Huaiying Zhang","doi":"10.1101/gad.351667.124","DOIUrl":"https://doi.org/10.1101/gad.351667.124","url":null,"abstract":"The alternative lengthening of telomeres (ALT) pathway maintains telomere length in a significant fraction of cancers that are associated with poor clinical outcomes. A better understanding of ALT mechanisms is therefore necessary for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins contributes to the formation of ALT telomere-associated PML bodies (APBs), in which telomeres are clustered and DNA repair proteins are enriched to promote homology-directed telomere DNA synthesis in ALT. However, it is still unknown whether—and if so, how—SUMO supports ALT beyond APB formation. Here, we show that SUMO condensates that contain DNA repair proteins enable telomere maintenance in the absence of APBs. In PML knockout ALT cell lines that lack APBs, we found that SUMOylation is required for manifesting ALT features independent of PML and APBs. Chemically induced telomere targeting of SUMO produces condensate formation and ALT features in PML-null cells. This effect requires both SUMOylation and interactions between SUMO and SUMO interaction motifs (SIMs). Mechanistically, SUMO-induced effects are associated with the accumulation of DNA repair proteins, including Rad52, Rad51AP1, RPA, and BLM, at telomeres. Furthermore, Rad52 can undergo phase separation, enrich SUMO at telomeres, and promote telomere DNA synthesis in collaboration with the BLM helicase in a SUMO-dependent manner. Collectively, our findings suggest that SUMO condensate formation promotes collaboration among DNA repair factors to support ALT telomere maintenance without PML. Given the promising effects of SUMOylation inhibitors in cancer treatment, our findings suggest their potential use in perturbing telomere maintenance in ALT cancer cells.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"35 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Structural and biochemical analyses of the nuclear IκBζ protein in complex with the NF-κB p50 homodimer. 核 IκBζ 蛋白与 NF-κB p50 同源二聚体复合物的结构和生化分析。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-07-19 DOI: 10.1101/gad.351892.124

Norman Zhu, W Eric Rogers, David K Heidary, Tom Huxford

引用次数: 0

Epigenetic modulators provide a path to understanding disease and therapeutic opportunity. 表观遗传调节剂提供了一条了解疾病和治疗机会的途径。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-07-19 DOI: 10.1101/gad.351444.123

Madison A Honer, Benjamin I Ferman, Zach H Gray, Elena A Bondarenko, Johnathan R Whetstine

引用次数: 0

Selective regulation of a defined subset of inflammatory and immunoregulatory genes by an NF-κB p50-IκBζ pathway. NF-κB p50-IκBζ 通路对特定亚群炎症和免疫调节基因的选择性调控。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-07-19 DOI: 10.1101/gad.351630.124

Allison E Daly, George Yeh, Sofia Soltero, Stephen T Smale

{"title":"Selective regulation of a defined subset of inflammatory and immunoregulatory genes by an NF-κB p50-IκBζ pathway.","authors":"Allison E Daly, George Yeh, Sofia Soltero, Stephen T Smale","doi":"10.1101/gad.351630.124","DOIUrl":"10.1101/gad.351630.124","url":null,"abstract":"The five NF-κB family members and three nuclear IκB proteins play important biological roles, but the mechanisms by which distinct members of these protein families contribute to selective gene transcription remain poorly understood, especially at a genome-wide scale. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent and IκBζ-dependent genes in Toll-like receptor 4 (TLR4)-activated macrophages. Key immunoregulatory genes, including Il6, Il1b, Nos2, Lcn2, and Batf, are among the p50-IκBζ-codependent genes. IκBζ-bound genomic sites are occupied at earlier time points by NF-κB dimers. However, p50-IκBζ codependence does not coincide with preferential binding of either p50 or IκBζ, as RelA co-occupies hundreds of genomic sites with the two proteins. A common feature of p50-IκBζ-codependent genes is a nearby p50/RelA/IκBζ-cobound site exhibiting p50-dependent binding of both RelA and IκBζ. This and other results suggest that IκBζ acts in concert with RelA:p50 heterodimers. Notably, p50-IκBζ-codependent genes comprise a high percentage of genes exhibiting the greatest differential expression between TLR4-stimulated and tumor necrosis factor receptor (TNFR)-stimulated macrophages. Thus, our genome-centric analysis reveals a defined p50-IκBζ pathway that selectively activates a set of key immunoregulatory genes and serves as an important contributor to differential TNFR and TLR4 responses.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"536-553"},"PeriodicalIF":7.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy. 表达 Tert 的细胞有助于唾液腺的平衡和放疗后的组织再生。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-07-19 DOI: 10.1101/gad.351577.124

Li Guan, Vignesh Viswanathan, Yuyan Jiang, Sivakamasundari Vijayakumar, Hongbin Cao, Junfei Zhao, Deana Rae Crystal Colburg, Patrick Neuhöfer, Yiru Zhang, Jinglong Wang, Yu Xu, Eyiwunmi E Laseinde, Rachel Hildebrand, Mobeen Rahman, Richard Frock, Christina Kong, Philip A Beachy, Steven Artandi, Quynh-Thu Le

{"title":"Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy.","authors":"Li Guan, Vignesh Viswanathan, Yuyan Jiang, Sivakamasundari Vijayakumar, Hongbin Cao, Junfei Zhao, Deana Rae Crystal Colburg, Patrick Neuhöfer, Yiru Zhang, Jinglong Wang, Yu Xu, Eyiwunmi E Laseinde, Rachel Hildebrand, Mobeen Rahman, Richard Frock, Christina Kong, Philip A Beachy, Steven Artandi, Quynh-Thu Le","doi":"10.1101/gad.351577.124","DOIUrl":"10.1101/gad.351577.124","url":null,"abstract":"Salivary gland homeostasis and regeneration after radiotherapy depend significantly on progenitor cells. However, the lineage of submandibular gland (SMG) progenitor cells remains less defined compared with other normal organs. Here, using a mouse strain expressing regulated CreERT2 recombinase from the endogenous Tert locus, we identify a distinct telomerase-expressing (TertHigh) cell population located in the ductal region of the adult SMG. These TertHigh cells contribute to ductal cell generation during SMG homeostasis and to both ductal and acinar cell renewal 1 year after radiotherapy. TertHigh cells maintain self-renewal capacity during in vitro culture, exhibit resistance to radiation damage, and demonstrate enhanced proliferative activity after radiation exposure. Similarly, primary human SMG cells with high Tert expression display enhanced cell survival after radiotherapy, and CRISPR-activated Tert in human SMG spheres increases proliferation after radiation. RNA sequencing reveals upregulation of \"cell cycling\" and \"oxidative stress response\" pathways in TertHigh cells following radiation. Mechanistically, Tert appears to modulate cell survival through ROS levels in SMG spheres following radiation damage. Our findings highlight the significance of TertHigh cells in salivary gland biology, providing insights into their response to radiotherapy and into their use as a potential target for enhancing salivary gland regeneration after radiotherapy.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"569-582"},"PeriodicalIF":7.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141599100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity. 作为 R 环抑制因子的 RNA 生物发生和 RNA 代谢因子：在基因组完整性中的隐性作用。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-07-19 DOI: 10.1101/gad.351853.124

Rosa Luna, Belén Gómez-González, Andrés Aguilera

引用次数: 0