Chromosome Research最新文献_第3页

Disentangling the roles of aneuploidy, chromosomal instability and tumour heterogeneity in developing resistance to cancer therapies. 阐明非整倍体、染色体不稳定性和肿瘤异质性在癌症治疗耐药性发展中的作用。

IF 2.6 4区生物学

Chromosome Research Pub Date : 2023-09-18 DOI: 10.1007/s10577-023-09737-5

Joana Reis Andrade, Annie Dinky Gallagher, Jovanna Maharaj, Sarah Elizabeth McClelland

{"title":"Disentangling the roles of aneuploidy, chromosomal instability and tumour heterogeneity in developing resistance to cancer therapies.","authors":"Joana Reis Andrade, Annie Dinky Gallagher, Jovanna Maharaj, Sarah Elizabeth McClelland","doi":"10.1007/s10577-023-09737-5","DOIUrl":"10.1007/s10577-023-09737-5","url":null,"abstract":"Aneuploidy is defined as the cellular state of having a number of chromosomes that deviates from a multiple of the normal haploid chromosome number of a given organism. Aneuploidy can be present in a static state: Down syndrome individuals stably maintain an extra copy of chromosome 21 in their cells. In cancer cells, however, aneuploidy is usually present in combination with chromosomal instability (CIN) which leads to a continual generation of new chromosomal alterations and the development of intratumour heterogeneity (ITH). The prevalence of cells with specific chromosomal alterations is further shaped by evolutionary selection, for example, during the administration of cancer therapies. Aneuploidy, CIN and ITH have each been individually associated with poor prognosis in cancer, and a wealth of evidence suggests they contribute, either alone or in combination, to cancer therapy resistance by providing a reservoir of potential resistant states, or the ability to rapidly evolve resistance. A full understanding of the contribution and interplay between aneuploidy, CIN and ITH is required to tackle therapy resistance in cancer patients. However, these characteristics often co-occur and are intrinsically linked, presenting a major challenge to defining their individual contributions. Moreover, their accurate measurement in both experimental and clinical settings is a technical hurdle. Here, we attempt to deconstruct the contribution of the individual and combined roles of aneuploidy, CIN and ITH to therapy resistance in cancer, and outline emerging approaches to measure and disentangle their roles as a step towards integrating these principles into cancer therapeutic strategy.","PeriodicalId":50698,"journal":{"name":"Chromosome Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10300478","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

Analog-sensitive Cdk1 as a tool to study mitotic exit: protein phosphatase 1 is required downstream from Cdk1 inactivation in budding yeast. 类似物敏感的Cdk1作为研究有丝分裂退出的工具：出芽酵母中Cdk1失活下游需要蛋白磷酸酶1。

IF 2.6 4区生物学

Chromosome Research Pub Date : 2023-09-10 DOI: 10.1007/s10577-023-09736-6

Jason M Keaton, Benjamin G Workman, Linfeng Xie, James R Paulson

{"title":"Analog-sensitive Cdk1 as a tool to study mitotic exit: protein phosphatase 1 is required downstream from Cdk1 inactivation in budding yeast.","authors":"Jason M Keaton, Benjamin G Workman, Linfeng Xie, James R Paulson","doi":"10.1007/s10577-023-09736-6","DOIUrl":"10.1007/s10577-023-09736-6","url":null,"abstract":"We show that specific inactivation of the protein kinase Cdk1/cyclin B (Cdc28/Clb2) triggers exit from mitosis in the budding yeast Saccharomyces cerevisiae. Cells carrying the allele cdc28-as1, which makes Cdk1 (Cdc28) uniquely sensitive to the ATP analog 1NM-PP1, were arrested with spindle poisons and then treated with 1NM-PP1 to inhibit Cdk1. This caused the cells to leave mitosis and enter G1-phase as shown by initiation of rebudding (without cytokinesis), induction of mating projections (\"shmoos\") by α-factor, stabilization of Sic1, and degradation of Clb2. It is known that Cdk1 must be inactivated for cells to exit mitosis, but our results show that inactivation of Cdk1 is not only necessary but also sufficient to initiate the transition from mitosis to G1-phase. This result suggests a system in which to test requirements for particular gene products downstream from Cdk1 inactivation, for example, by combining cdc28-as1 with conditional mutations in the genes of interest. Using this approach, we demonstrate that protein phosphatase 1 (PPase1; Glc7 in S. cerevisiae) is required for mitotic exit and reestablishment of interphase following Cdk1 inactivation. This system could be used to test the need for other protein phosphatases downstream from Cdk1 inactivation, such as PPase 2A and Cdc14, and it could be combined with phosphoproteomics to gain information about the substrates that the various phosphatases act upon during mitotic exit.","PeriodicalId":50698,"journal":{"name":"Chromosome Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10596320","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

Meiotic segregation and post-meiotic drive of the Festuca pratensis B chromosome. 高羊茅B染色体的减数分裂和减数分裂后驱动。

IF 2.6 4区生物学

Chromosome Research Pub Date : 2023-09-02 DOI: 10.1007/s10577-023-09728-6

Rahman Ebrahimzadegan, Jörg Fuchs, Jianyong Chen, Veit Schubert, Armin Meister, Andreas Houben, Ghader Mirzaghaderi

{"title":"Meiotic segregation and post-meiotic drive of the Festuca pratensis B chromosome.","authors":"Rahman Ebrahimzadegan, Jörg Fuchs, Jianyong Chen, Veit Schubert, Armin Meister, Andreas Houben, Ghader Mirzaghaderi","doi":"10.1007/s10577-023-09728-6","DOIUrl":"10.1007/s10577-023-09728-6","url":null,"abstract":"In many species, the transmission of B chromosomes (Bs) does not follow the Mendelian laws of equal segregation and independent assortment. This deviation results in transmission rates of Bs higher than 0.5, a process known as \"chromosome drive\". Here, we studied the behavior of the 103 Mbp-large B chromosome of Festuca pratensis during all meiotic and mitotic stages of microsporogenesis. Mostly, the B chromosome of F. pratensis segregates during meiosis like standard A chromosomes (As). In some cases, the B passes through meiosis in a non-Mendelian segregation leading to their accumulation already in meiosis. However, a true drive of the B happens during the first pollen mitosis, by which the B preferentially migrates to the generative nucleus. During second pollen mitosis, B divides equally between the two sperms. Despite some differences in the frequency of drive between individuals with different numbers of Bs, at least 82% of drive was observed. Flow cytometry-based quantification of B-containing sperm nuclei agrees with the FISH data.","PeriodicalId":50698,"journal":{"name":"Chromosome Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161451","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

Modeling specific aneuploidies: from karyotype manipulations to biological insights. 特定非整倍体的建模：从核型操作到生物学见解。

IF 2.4 4区生物学

Chromosome Research Pub Date : 2023-08-29 DOI: 10.1007/s10577-023-09735-7

My Anh Truong, Paula Cané-Gasull, Susanne M A Lens

引用次数: 0

Consequences of gaining an extra chromosome. 获得额外染色体的后果。

IF 2.4 4区生物学

Chromosome Research Pub Date : 2023-08-25 DOI: 10.1007/s10577-023-09732-w

Eduardo M Torres

{"title":"Consequences of gaining an extra chromosome.","authors":"Eduardo M Torres","doi":"10.1007/s10577-023-09732-w","DOIUrl":"10.1007/s10577-023-09732-w","url":null,"abstract":"Mistakes in chromosome segregation leading to aneuploidy are the primary cause of miscarriages in humans. Excluding sex chromosomes, viable aneuploidies in humans include trisomies of chromosomes 21, 18, or 13, which cause Down, Edwards, or Patau syndromes, respectively. While individuals with trisomy 18 or 13 die soon after birth, people with Down syndrome live to adulthood but have intellectual disabilities and are prone to multiple diseases. At the cellular level, mistakes in the segregation of a single chromosome leading to a cell losing a chromosome are lethal. In contrast, the cell that gains a chromosome can survive. Several studies support the hypothesis that gaining an extra copy of a chromosome causes gene-specific phenotypes and phenotypes independent of the identity of the genes encoded within that chromosome. The latter, referred to as aneuploidy-associated phenotypes, are the focus of this review. Among the conserved aneuploidy-associated phenotypes observed in yeast and human cells are lower viability, increased gene expression, increased protein synthesis and turnover, abnormal nuclear morphology, and altered metabolism. Notably, abnormal nuclear morphology of aneuploid cells is associated with increased metabolic demand for de novo synthesis of sphingolipids. These findings reveal important insights into the possible pathological role of aneuploidy in Down syndrome. Despite the adverse effects on cell physiology, aneuploidy is a hallmark of cancer cells. Understanding how aneuploidy affects cell physiology can reveal insights into the selective pressure that aneuploid cancer cells must overcome to support unlimited proliferation.","PeriodicalId":50698,"journal":{"name":"Chromosome Research","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10503949","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

Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells. 复制应激导致人类诱导多能干细胞中ANKS1B大神经元基因的有丝分裂进入延迟和12号染色体脆性。

IF 2.6 4区生物学

Chromosome Research Pub Date : 2023-08-19 DOI: 10.1007/s10577-023-09729-5

Anastasiia V Kislova, Diana Zheglo, Victoria O Pozhitnova, Philipp S Sviridov, Elmira P Gadzhieva, Ekaterina S Voronina

{"title":"Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells.","authors":"Anastasiia V Kislova, Diana Zheglo, Victoria O Pozhitnova, Philipp S Sviridov, Elmira P Gadzhieva, Ekaterina S Voronina","doi":"10.1007/s10577-023-09729-5","DOIUrl":"10.1007/s10577-023-09729-5","url":null,"abstract":"Substantial background level of replication stress is a feature of embryonic and induced pluripotent stem cells (iPSCs), which can predispose to numerical and structural chromosomal instability, including recurrent aberrations of chromosome 12. In differentiated cells, replication stress-sensitive genomic regions, including common fragile sites, are widely mapped through mitotic chromosome break induction by mild aphidicolin treatment, an inhibitor of replicative polymerases. IPSCs exhibit lower apoptotic threshold and higher repair capacity hindering fragile site mapping. Caffeine potentiates genotoxic effects and abrogates G2/M checkpoint delay induced by chemical and physical mutagens. Using 5-ethynyl-2'-deoxyuridine (EdU) for replication labeling, we characterized the mitotic entry dynamics of asynchronous iPSCs exposed to aphidicolin and/or caffeine. Under the adjusted timing of replication stress exposure accounting revealed cell cycle delay, higher metaphase chromosome breakage rate was observed in iPSCs compared to primary lymphocytes. Using differential chromosome staining and subsequent locus-specific fluorescent in situ hybridization, we mapped the FRA12L fragile site spanning the large neuronal ANKS1B gene at 12q23.1, which may contribute to recurrent chromosome 12 missegregation and rearrangements in iPSCs. Publicly available data on the ANKS1B genetic alterations and their possible functional impact are reviewed. Our study provides the first evidence of common fragile site induction in iPSCs and reveals potential somatic instability of a clinically relevant gene during early human development and in vitro cell expansion.","PeriodicalId":50698,"journal":{"name":"Chromosome Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10141129","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: 1

Genome composition in Brassica interspecific hybrids affects chromosome inheritance and viability of progeny. 芸苔属种间杂交种的基因组组成影响后代的染色体遗传和活力。

IF 2.6 4区生物学

Chromosome Research Pub Date : 2023-08-19 DOI: 10.1007/s10577-023-09733-9

Elvis Katche, Elizabeth Ihien Katche, Paula Vasquez-Teuber, Zurianti Idris, Yu-Tzu Lo, David Nugent, Jun Zou, Jacqueline Batley, Annaliese S Mason

{"title":"Genome composition in Brassica interspecific hybrids affects chromosome inheritance and viability of progeny.","authors":"Elvis Katche, Elizabeth Ihien Katche, Paula Vasquez-Teuber, Zurianti Idris, Yu-Tzu Lo, David Nugent, Jun Zou, Jacqueline Batley, Annaliese S Mason","doi":"10.1007/s10577-023-09733-9","DOIUrl":"10.1007/s10577-023-09733-9","url":null,"abstract":"Interspecific hybridization is widespread in nature and can result in the formation of new hybrid species as well as the transfer of traits between species. However, the fate of newly formed hybrid lineages is relatively understudied. We undertook pairwise crossing between multiple genotypes of three Brassica allotetraploid species Brassica juncea (2n = AABB), Brassica carinata (2n = BBCC), and Brassica napus (2n = AACC) to generate AABC, BBAC, and CCAB interspecific hybrids and investigated chromosome inheritance and fertility in these hybrids and their self-pollinated progeny. Surprisingly, despite the presence of a complete diploid genome in all hybrids, hybrid fertility was very low. AABC and BBAC first generation (F1) hybrids both averaged ~16% pollen viability compared to 3.5% in CCAB hybrids: most CCAB hybrid flowers were male-sterile. AABC and CCAB F1 hybrid plants averaged 5.5 and 0.5 seeds per plant, respectively, and BBAC F1 hybrids ~56 seeds/plant. In the second generation (S1), all confirmed self-pollinated progeny resulting from CCAB hybrids were sterile, producing no self-pollinated seeds. Three AABC S1 hybrids putatively resulting from unreduced gametes produced 3, 14, and 182 seeds each, while other AABC S1 hybrids averaged 1.5 seeds/plant (0-8). BBAC S1 hybrids averaged 44 seeds/plant (range 0-403). We also observed strong bias towards retention rather than loss of the haploid genomes, suggesting that the subgenomes in the Brassica allotetraploids are already highly interdependent, such that loss of one subgenome is detrimental to fertility and viability. Our results suggest that relationships between subgenomes determine hybridization outcomes in these species.","PeriodicalId":50698,"journal":{"name":"Chromosome Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10147736","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

Correction to: Human artificial chromosome carrying 3p21.3‑p22.2 region suppresses hTERT transcription in oral cancer cells. 更正：携带3p21.3‑p22.2区域的人类人工染色体抑制口腔癌症细胞中hTERT转录。

IF 2.6 4区生物学

Chromosome Research Pub Date : 2023-08-17 DOI: 10.1007/s10577-023-09734-8

Takahito Ohira, Kaho Yoshimura, Hiroyuki Kugoh

引用次数: 0

Exploiting a living biobank to delineate mechanisms underlying disease-specific chromosome instability. 利用活体生物库来描述疾病特异性染色体不稳定的潜在机制。

IF 2.6 4区生物学

Chromosome Research Pub Date : 2023-08-17 DOI: 10.1007/s10577-023-09731-x

Louisa Nelson, Bethany M Barnes, Anthony Tighe, Samantha Littler, Camilla Coulson-Gilmer, Anya Golder, Sudha Desai, Robert D Morgan, Joanne C McGrail, Stephen S Taylor

{"title":"Exploiting a living biobank to delineate mechanisms underlying disease-specific chromosome instability.","authors":"Louisa Nelson, Bethany M Barnes, Anthony Tighe, Samantha Littler, Camilla Coulson-Gilmer, Anya Golder, Sudha Desai, Robert D Morgan, Joanne C McGrail, Stephen S Taylor","doi":"10.1007/s10577-023-09731-x","DOIUrl":"10.1007/s10577-023-09731-x","url":null,"abstract":"Chromosome instability (CIN) is a cancer hallmark that drives tumour heterogeneity, phenotypic adaptation, drug resistance and poor prognosis. High-grade serous ovarian cancer (HGSOC), one of the most chromosomally unstable tumour types, has a 5-year survival rate of only ~30% - largely due to late diagnosis and rapid development of drug resistance, e.g., via CIN-driven ABCB1 translocations. However, CIN is also a cell cycle vulnerability that can be exploited to specifically target tumour cells, illustrated by the success of PARP inhibitors to target homologous recombination deficiency (HRD). However, a lack of appropriate models with ongoing CIN has been a barrier to fully exploiting disease-specific CIN mechanisms. This barrier is now being overcome with the development of patient-derived cell cultures and organoids. In this review, we describe our progress building a Living Biobank of over 120 patient-derived ovarian cancer models (OCMs), predominantly from HGSOC. OCMs are highly purified tumour fractions with extensive proliferative potential that can be analysed at early passage. OCMs have diverse karyotypes, display intra- and inter-patient heterogeneity and mitotic abnormality rates far higher than established cell lines. OCMs encompass a broad-spectrum of HGSOC hallmarks, including a range of p53 alterations and BRCA1/2 mutations, and display drug resistance mechanisms seen in the clinic, e.g., ABCB1 translocations and BRCA2 reversion. OCMs are amenable to functional analysis, drug-sensitivity profiling, and multi-omics, including single-cell next-generation sequencing, and thus represent a platform for delineating HGSOC-specific CIN mechanisms. In turn, our vision is that this understanding will inform the design of new therapeutic strategies.","PeriodicalId":50698,"journal":{"name":"Chromosome Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10503487","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

Chromosomal instability and inflammation: a catch-22 for cancer cells. 染色体不稳定和炎症：癌症细胞的第二十二条军规。

IF 2.6 4区生物学

Chromosome Research Pub Date : 2023-08-10 DOI: 10.1007/s10577-023-09730-y

Anouk van den Brink, Maria F Suárez Peredo Rodríguez, Floris Foijer

{"title":"Chromosomal instability and inflammation: a catch-22 for cancer cells.","authors":"Anouk van den Brink, Maria F Suárez Peredo Rodríguez, Floris Foijer","doi":"10.1007/s10577-023-09730-y","DOIUrl":"10.1007/s10577-023-09730-y","url":null,"abstract":"Chromosomal instability (CIN), an increased rate of chromosomal segregation abnormalities, drives intratumor heterogeneity and affects most human cancers. In addition to chromosome copy number alterations, CIN results in chromosome(s) (fragments) being mislocalized into the cytoplasm in the form of micronuclei. Micronuclei can be detected by cGAS, a double-strand nucleic acid sensor, which will lead to the production of the second messenger 2'3'-cGAMP, activation of an inflammatory response, and downstream immune cell activation. However, the molecular network underlying the CIN-induced inflammatory response is still poorly understood. Furthermore, there is emerging evidence that cancers that display CIN circumvent this CIN-induced inflammatory response, and thus immune surveillance. The STAT1, STAT3, and NF-κB signaling cascades appear to play an important role in the CIN-induced inflammatory response. In this review, we discuss how these pathways are involved in signaling CIN in cells and how they are intertwined. A better understanding of how CIN is being signaled in cells and how cancer cells circumvent this is of the utmost importance for better and more selective cancer treatment.","PeriodicalId":50698,"journal":{"name":"Chromosome Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152605","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