Chromosoma最新文献_第3页

Genome maintenance meets mechanobiology. 基因组维护与机械生物学的结合

IF 2.5 4区生物学

Chromosoma Pub Date : 2024-01-01 Epub Date: 2023-08-15 DOI: 10.1007/s00412-023-00807-5

Vincent Spegg, Matthias Altmeyer

{"title":"Genome maintenance meets mechanobiology.","authors":"Vincent Spegg, Matthias Altmeyer","doi":"10.1007/s00412-023-00807-5","DOIUrl":"10.1007/s00412-023-00807-5","url":null,"abstract":"Genome stability is key for healthy cells in healthy organisms, and deregulated maintenance of genome integrity is a hallmark of aging and of age-associated diseases including cancer and neurodegeneration. To maintain a stable genome, genome surveillance and repair pathways are closely intertwined with cell cycle regulation and with DNA transactions that occur during transcription and DNA replication. Coordination of these processes across different time and length scales involves dynamic changes of chromatin topology, clustering of fragile genomic regions and repair factors into nuclear repair centers, mobilization of the nuclear cytoskeleton, and activation of cell cycle checkpoints. Here, we provide a general overview of cell cycle regulation and of the processes involved in genome duplication in human cells, followed by an introduction to replication stress and to the cellular responses elicited by perturbed DNA synthesis. We discuss fragile genomic regions that experience high levels of replication stress, with a particular focus on telomere fragility caused by replication stress at the ends of linear chromosomes. Using alternative lengthening of telomeres (ALT) in cancer cells and ALT-associated PML bodies (APBs) as examples of replication stress-associated clustered DNA damage, we discuss compartmentalization of DNA repair reactions and the role of protein properties implicated in phase separation. Finally, we highlight emerging connections between DNA repair and mechanobiology and discuss how biomolecular condensates, components of the nuclear cytoskeleton, and interfaces between membrane-bound organelles and membraneless macromolecular condensates may cooperate to coordinate genome maintenance in space and time.","PeriodicalId":10248,"journal":{"name":"Chromosoma","volume":" ","pages":"15-36"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10001098","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

Genetic heterogeneity in p53-null leukemia increases transiently with spindle assembly checkpoint inhibition and is not rescued by p53. p53 基因缺失白血病的遗传异质性会随着纺锤体组装检查点的抑制而短暂增加，但 p53 并不能挽救这种异质性。

IF 2.5 4区生物学

Chromosoma Pub Date : 2024-01-01 Epub Date: 2023-05-31 DOI: 10.1007/s00412-023-00800-y

Mai Wang, Steven Phan, Brandon H Hayes, Dennis E Discher

{"title":"Genetic heterogeneity in p53-null leukemia increases transiently with spindle assembly checkpoint inhibition and is not rescued by p53.","authors":"Mai Wang, Steven Phan, Brandon H Hayes, Dennis E Discher","doi":"10.1007/s00412-023-00800-y","DOIUrl":"10.1007/s00412-023-00800-y","url":null,"abstract":"Chromosome gains or losses often lead to copy number variations (CNV) and loss of heterozygosity (LOH). Both quantities are low in hematologic \"liquid\" cancers versus solid tumors in data of The Cancer Genome Atlas (TCGA) that also shows the fraction of a genome affected by LOH is ~ one-half of that with CNV. Suspension cultures of p53-null THP-1 leukemia-derived cells conform to these trends, despite novel evidence here of genetic heterogeneity and transiently elevated CNV after perturbation. Single-cell DNAseq indeed reveals at least 8 distinct THP-1 aneuploid clones with further intra-clonal variation, suggesting ongoing genetic evolution. Importantly, acute inhibition of the mitotic spindle assembly checkpoint (SAC) produces CNV levels that are typical of high-CNV solid tumors, with subsequent cell death and down-selection to novel CNV. Pan-cancer analyses show p53 inactivation associates with aneuploidy, but leukemias exhibit a weaker trend even though p53 inactivation correlates with poor survival. Overexpression of p53 in THP-1 does not rescue established aneuploidy or LOH but slightly increases cell death under oxidative or confinement stress, and triggers p21, a key p53 target, but without affecting net growth. Our results suggest that factors other than p53 exert stronger pressures against aneuploidy in liquid cancers, and identifying such CNV suppressors could be useful across liquid and solid tumor types.","PeriodicalId":10248,"journal":{"name":"Chromosoma","volume":" ","pages":"77-92"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9548545","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

Histone FRET reports the spatial heterogeneity in nanoscale chromatin architecture that is imparted by the epigenetic landscape at the level of single foci in an intact cell nucleus. 组蛋白 FRET 报告了纳米级染色质结构的空间异质性，这种异质性是由完整细胞核中单个病灶水平上的表观遗传景观赋予的。

IF 1.6 4区生物学

Chromosoma Pub Date : 2024-01-01 Epub Date: 2024-01-24 DOI: 10.1007/s00412-024-00815-z

Zhen Liang, Ashleigh Solano, Jieqiong Lou, Elizabeth Hinde

{"title":"Histone FRET reports the spatial heterogeneity in nanoscale chromatin architecture that is imparted by the epigenetic landscape at the level of single foci in an intact cell nucleus.","authors":"Zhen Liang, Ashleigh Solano, Jieqiong Lou, Elizabeth Hinde","doi":"10.1007/s00412-024-00815-z","DOIUrl":"10.1007/s00412-024-00815-z","url":null,"abstract":"Genome sequencing has identified hundreds of histone post-translational modifications (PTMs) that define an open or compact chromatin nanostructure at the level of nucleosome proximity, and therefore serve as activators or repressors of gene expression. Direct observation of this epigenetic mode of transcriptional regulation in an intact single nucleus, is however, a complex task. This is because despite the development of fluorescent probes that enable observation of specific histone PTMs and chromatin density, the changes in nucleosome proximity regulating gene expression occur on a spatial scale well below the diffraction limit of optical microscopy. In recent work, to address this research gap, we demonstrated that the phasor approach to fluorescence lifetime imaging microscopy (FLIM) of Förster resonance energy transfer (FRET) between fluorescently labelled histones core to the nucleosome, is a readout of chromatin nanostructure that can be multiplexed with immunofluorescence (IF) against specific histone PTMs. Here from application of this methodology to gold standard gene activators (H3K4Me3 and H3K9Ac) versus repressors (e.g., H3K9Me3 and H3K27Me), we find that while on average these histone marks do impart an open versus compact chromatin nanostructure, at the level of single chromatin foci, there is significant spatial heterogeneity. Collectively this study illustrates the importance of studying the epigenetic landscape as a function of space within intact nuclear architecture and opens the door for the study of chromatin foci sub-populations defined by combinations of histone marks, as is seen in the context of bivalent chromatin.","PeriodicalId":10248,"journal":{"name":"Chromosoma","volume":" ","pages":"5-14"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541694","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

DNA replication and replication stress response in the context of nuclear architecture. 核结构背景下的 DNA 复制和复制应激反应。

IF 2.5 4区生物学

Chromosoma Pub Date : 2024-01-01 Epub Date: 2023-12-06 DOI: 10.1007/s00412-023-00813-7

Daniel González-Acosta, Massimo Lopes

{"title":"DNA replication and replication stress response in the context of nuclear architecture.","authors":"Daniel González-Acosta, Massimo Lopes","doi":"10.1007/s00412-023-00813-7","DOIUrl":"10.1007/s00412-023-00813-7","url":null,"abstract":"The DNA replication process needs to be coordinated with other DNA metabolism transactions and must eventually extend to the full genome, regardless of chromatin status, gene expression, secondary structures and DNA lesions. Completeness and accuracy of DNA replication are crucial to maintain genome integrity, limiting transformation in normal cells and offering targeting opportunities for proliferating cancer cells. DNA replication is thus tightly coordinated with chromatin dynamics and 3D genome architecture, and we are only beginning to understand the underlying molecular mechanisms. While much has recently been discovered on how DNA replication initiation is organised and modulated in different genomic regions and nuclear territories-the so-called \"DNA replication program\"-we know much less on how the elongation of ongoing replication forks and particularly the response to replication obstacles is affected by the local nuclear organisation. Also, it is still elusive how specific components of nuclear architecture participate in the replication stress response. Here, we review known mechanisms and factors orchestrating replication initiation, and replication fork progression upon stress, focusing on recent evidence linking genome organisation and nuclear architecture with the cellular responses to replication interference, and highlighting open questions and future challenges to explore this exciting new avenue of research.","PeriodicalId":10248,"journal":{"name":"Chromosoma","volume":" ","pages":"57-75"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486845","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

Looping out of control: R-loops in transcription-replication conflict. 循环失控:转录-复制冲突中的r -环。

IF 2.5 4区生物学

Chromosoma Pub Date : 2024-01-01 Epub Date: 2023-07-07 DOI: 10.1007/s00412-023-00804-8

Charanya Kumar, Dirk Remus

{"title":"Looping out of control: R-loops in transcription-replication conflict.","authors":"Charanya Kumar, Dirk Remus","doi":"10.1007/s00412-023-00804-8","DOIUrl":"10.1007/s00412-023-00804-8","url":null,"abstract":"Transcription-replication conflict is a major cause of replication stress that arises when replication forks collide with the transcription machinery. Replication fork stalling at sites of transcription compromises chromosome replication fidelity and can induce DNA damage with potentially deleterious consequences for genome stability and organismal health. The block to DNA replication by the transcription machinery is complex and can involve stalled or elongating RNA polymerases, promoter-bound transcription factor complexes, or DNA topology constraints. In addition, studies over the past two decades have identified co-transcriptional R-loops as a major source for impairment of DNA replication forks at active genes. However, how R-loops impede DNA replication at the molecular level is incompletely understood. Current evidence suggests that RNA:DNA hybrids, DNA secondary structures, stalled RNA polymerases, and condensed chromatin states associated with R-loops contribute to the of fork progression. Moreover, since both R-loops and replication forks are intrinsically asymmetric structures, the outcome of R-loop-replisome collisions is influenced by collision orientation. Collectively, the data suggest that the impact of R-loops on DNA replication is highly dependent on their specific structural composition. Here, we will summarize our current understanding of the molecular basis for R-loop-induced replication fork progression defects.","PeriodicalId":10248,"journal":{"name":"Chromosoma","volume":" ","pages":"37-56"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10771546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751441","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

Cross-species chromosome painting and repetitive DNA mapping illuminate the karyotype evolution in true crocodiles (Crocodylidae). 跨物种染色体绘制和重复DNA图谱揭示了真鳄鱼（鳄科）的核型进化。

IF 1.6 4区生物学

Chromosoma Pub Date : 2023-11-01 Epub Date: 2023-07-26 DOI: 10.1007/s00412-023-00806-6

Vanessa Sales-Oliveira, Marie Altmanová, Václav Gvoždík, Rafael Kretschmer, Tariq Ezaz, Thomas Liehr, Niklas Padutsch, Gabriel Badjedjea, Ricardo Utsunomia, Alongklod Tanomtong, Marcelo Cioffi

{"title":"Cross-species chromosome painting and repetitive DNA mapping illuminate the karyotype evolution in true crocodiles (Crocodylidae).","authors":"Vanessa Sales-Oliveira, Marie Altmanová, Václav Gvoždík, Rafael Kretschmer, Tariq Ezaz, Thomas Liehr, Niklas Padutsch, Gabriel Badjedjea, Ricardo Utsunomia, Alongklod Tanomtong, Marcelo Cioffi","doi":"10.1007/s00412-023-00806-6","DOIUrl":"10.1007/s00412-023-00806-6","url":null,"abstract":"Crocodilians have maintained very similar karyotype structures and diploid chromosome numbers for around 100 million years, with only minor variations in collinearity. Why this karyotype structure has largely stayed unaltered for so long is unclear. In this study, we analyzed the karyotypes of six species belonging to the genera Crocodylus and Osteolaemus (Crocodylidae, true crocodiles), among which the Congolian endemic O. osborni was included and investigated. We utilized various techniques (differential staining, fluorescence in situ hybridization with repetitive DNA and rDNA probes, whole chromosome painting, and comparative genomic hybridization) to better understand how crocodile chromosomes evolved. We studied representatives of three of the four main diploid chromosome numbers found in crocodiles (2n = 30/32/38). Our data provided new information about the species studied, including the identification of four major chromosomal rearrangements that occurred during the karyotype diversification process in crocodiles. These changes led to the current diploid chromosome numbers of 2n = 30 (fusion) and 2n = 38 (fissions), derived from the ancestral state of 2n = 32. The conserved cytogenetic tendency in crocodilians, where extant species keep near-ancestral state, contrasts with the more dynamic karyotype evolution seen in other major reptile groups.","PeriodicalId":10248,"journal":{"name":"Chromosoma","volume":" ","pages":"289-303"},"PeriodicalIF":1.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247932","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

Nucleolin is required for multiple centrosome-associated functions in early vertebrate mitosis. 在脊椎动物早期有丝分裂过程中，需要 Nucleolin 发挥与中心体相关的多种功能。

IF 1.6 4区生物学

Chromosoma Pub Date : 2023-11-01 Epub Date: 2023-08-24 DOI: 10.1007/s00412-023-00808-4

Chandan Kumar, Sivaram V S Mylavarapu

引用次数: 0

H3K9 and H4K20 methyltransferases are directly involved in the heterochromatinization of the paternal chromosomes in male Planococcus citri embryos. H3K9和H4K20甲基转移酶直接参与了雄性柠檬扁球菌胚胎中父系染色体的异染色化。

IF 1.6 4区生物学

Chromosoma Pub Date : 2023-11-01 Epub Date: 2023-09-12 DOI: 10.1007/s00412-023-00809-3

Yakov A Osipov, Olga V Posukh, Darya A Kalashnikova, Polina A Antoshina, Petr P Laktionov, Polina A Skrypnik, Stepan N Belyakin, Prim B Singh

引用次数: 0

Karyotypes of water frogs from the Pelophylax esculentus complex: results of cross-species chromosomal painting. 水蛙复合体的核型:跨种染色体绘制的结果。

IF 1.6 4区生物学

Chromosoma Pub Date : 2023-11-01 Epub Date: 2023-11-25 DOI: 10.1007/s00412-023-00812-8

Dmitrij Dedukh, Antonina Maslova, Ahmed Al-Rikabi, Niklas Padutsch, Thomas Liehr, Alla Krasikova

{"title":"Karyotypes of water frogs from the Pelophylax esculentus complex: results of cross-species chromosomal painting.","authors":"Dmitrij Dedukh, Antonina Maslova, Ahmed Al-Rikabi, Niklas Padutsch, Thomas Liehr, Alla Krasikova","doi":"10.1007/s00412-023-00812-8","DOIUrl":"10.1007/s00412-023-00812-8","url":null,"abstract":"Amphibian species have the largest genome size enriched with repetitive sequences and relatively similar karyotypes. Moreover, many amphibian species frequently hybridize causing nuclear and mitochondrial genome introgressions. In addition, hybridization in some amphibian species may lead to clonality and polyploidization. All such events were found in water frogs from the genus Pelophylax. Among the species within the genus Pelophylax, P. esculentus complex is the most widely distributed and well-studied. This complex includes two parental species, P. ridibundus and P. lessonae, and their hybrids, P. esculentus, reproducing hemiclonally. Parental species and their hybrids have similar but slightly polymorphic karyotypes, so their precise identification is still required. Here, we have developed a complete set of 13 chromosome painting probes for two parental species allowing the precise identification of all chromosomes. Applying chromosomal painting, we identified homologous chromosomes in both parental species and orthologous chromosomes in their diploid hemiclonal hybrids. Comparative painting did not reveal interchromosomal exchanges between the studied water frog species and their hybrids. Using cross-specific chromosome painting, we detected unequal distribution of the signals along chromosomes suggesting the presence of species-specific tandem repeats. Application of chromosomal paints to the karyotypes of hybrids revealed differences in the intensity of staining for P. ridibundus and P. lessonae chromosomes. Thus, both parental genomes have a divergence in unique sequences. Obtained chromosome probes may serve as a powerful tool to unravel chromosomal evolution in phylogenetically related species, identify individual chromosomes in different cell types, and investigate the elimination of chromosomes in hybrid water frogs.","PeriodicalId":10248,"journal":{"name":"Chromosoma","volume":" ","pages":"329-342"},"PeriodicalIF":1.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138433514","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

The regulation of Tfh cell differentiation by β-hydroxybutyrylation modification of transcription factor Bcl6. 转录因子 Bcl6 的β-羟基丁酰化修饰对 Tfh 细胞分化的调控。

IF 1.6 4区生物学

Chromosoma Pub Date : 2023-11-01 Epub Date: 2023-05-25 DOI: 10.1007/s00412-023-00799-2

Jingtian Guo, Yimeng Wang, Lei Tang, Tiejun Tang, Zhuolan Li, Mengyuan Li, Liming Wang, Aizhong Zeng, Yuxiao Ma, Shihao Huang, Xiaomeng Jiang, Wei Guo

{"title":"The regulation of Tfh cell differentiation by β-hydroxybutyrylation modification of transcription factor Bcl6.","authors":"Jingtian Guo, Yimeng Wang, Lei Tang, Tiejun Tang, Zhuolan Li, Mengyuan Li, Liming Wang, Aizhong Zeng, Yuxiao Ma, Shihao Huang, Xiaomeng Jiang, Wei Guo","doi":"10.1007/s00412-023-00799-2","DOIUrl":"10.1007/s00412-023-00799-2","url":null,"abstract":"Transcriptional repressor B cell lymphoma 6 (Bcl6) is a major transcription factor involved in Tfh cell differentiation and germinal center response, which is regulated by a variety of biological processes. However, the functional impact of post-translational modifications, particularly lysine β-hydroxybutyrylation (Kbhb), on Bcl6 remains elusive. In this study, we revealed that Bcl6 is modified by Kbhb to affect Tfh cell differentiation, resulting in the decrease of cell population and cytokine IL-21. Furthermore, the modification sites are identified from enzymatic reactions to be lysine residues at positions 376, 377, and 379 by mass spectrometry, which is confirmed by site-directed mutagenesis and functional analyses. Collectively, our present study provides evidence on the Kbhb modification of Bcl6 and also generates new insights into the regulation of Tfh cell differentiation, which is a starting point for a thorough understanding of the functional involvement of Kbhb modification in the differentiations of Tfh and other T cells.","PeriodicalId":10248,"journal":{"name":"Chromosoma","volume":" ","pages":"257-268"},"PeriodicalIF":1.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9895388","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