Biology subjects

Cetin, M.

Publications and source records attributed to Cetin, M..

4 recordsLinked to original sources

bioRxiv2022

Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2.

DEK has a short isoform (DEK isoform-2; DEK2) that lacks amino acid residues between 49-82. The full-length DEK (DEK isoform-1; DEK1) is ubiquitously expressed and plays a role in different cellular processes but whether DEK2 is involved in these processes remains elusive. We stably overexpressed DEK2 in human bone marrow stromal cell line HS-27A, in which endogenous DEKs were intact or suppressed via short hairpin RNA (sh-RNA). We have found that contrary to ectopic DEK1, DEK2 locates in the nucleus and nucleolus, causes persistent {gamma}H2AX signal upon doxorubicin treatment, and couldnt functionally compensate for the loss of DEK1. In addition, DEK2 overexpressing cells were more sensitive to doxorubicin than DEK1-cells. Expressions of DEK1 and DEK2 in cell lines and primary tumors exhibit tissue specificity. DEK1 is upregulated in cancers of the colon, liver, and lung compared to normal tissues while both DEK1 and DEK2 are downregulated in subsets of kidney, prostate, and thyroid carcinomas. Interestingly, only DEK2 was downregulated in a subset of breast tumors suggesting that DEK2 can be modulated differently than DEK1 in specific cancers. In summary, our findings show distinct expression patterns and subcellular location and suggest non-overlapping functions between the two DEK isoforms.

cell biology↗

bioRxiv2022

Targeting TACC3 represents a novel vulnerability in highly aggressive breast cancers with centrosome amplification

Centrosome amplification (CA) is a hallmark of cancer that is strongly associated with highly aggressive disease and worse clinical outcome. However, there are no effective strategies targeting cancer cells with CA while sparing normal cells. Here, we identified Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) to be overexpressed in tumors with CA, and its high expression is associated with dramatically worse clinical outcome. We demonstrated that TACC3 forms distinct functional interactions in mitotic and non-mitotic cancer cells with CA to facilitate centrosome clustering (CC) and transcriptional repression of tumor suppressors, respectively. We showed, for the first time, that TACC3 interacts with the Kinesin Family Member C1 (KIFC1) via its TACC domain in mitotic cells with CA and inhibition of TACC3 blocks this interaction, leading to apoptosis via multipolar spindle formation and activation of spindle assembly checkpoint (SAC)/CDK1/p-Bcl2 axis. In interphase, TACC3 interacts with the members of the nucleosome remodeling and deacetylase (NuRD) complex (HDAC2 and MBD2) in nucleus, and its inhibition causes p53-independent G1 arrest and apoptosis by blocking these interactions and activating the transcription of key tumor suppressors (e.g., p21, p16 and APAF1). Notably, inducing CA by chemical (cytochalasin D) or genomic (PLK4 overexpression or p53 loss) modulations renders cancer cells highly sensitive to TACC3 inhibition. Targeting TACC3 by small molecule inhibitors or guide RNAs strongly inhibits growth of organoids and breast cancer cell line- and patient-derived xenografts with CA. Altogether our results pave the way towards therapeutic targeting of TACC3 in highly aggressive cancers.

cancer biology↗

bioRxiv2021

New Insights into Molecular Basis Identification of Three Novel Strains of the Bacillus Subtilis Group Produce Cry Proteins Isolated from Soil Samples in Adana, Turkey

AimsThis study aimed to analyze the evolutionary relationship between Bacillus species isolated from agricultural soil using in-silico tools. Methods and ResultsAcross-sectional study was conducted in Adana province, in Turkey. A total of 120 Bacillus species were isolated from 80 soil samples. However, the phylogenetic tree diverged into two lineages; one belongs to B. subtilis group while the other belongs to B. cereus group. Interestingly, three native strains (SY27.1A, SY35.3A, and SY58.5A), which produce Cry proteins, shared high similarity with B. subtilis group (over 99%) and less than 95% similarity with known B. thuringiensis and other species of B. cereus group. Furthermore, 11 canonical SNPs (canSNPs) were identified in strains that belong to B. pumilus group when compared with B. subtilis reference sequences. ConclusionsPhylogenetic analysis of 16S rRNA sequences was found valuable for differentiation between Bacillus species isolated from soil samples. In addition, SNPs analysis provided more intra-specific information in the cases of B. subtilis group. Significance and Impact of StudyA detailed analysis was provided for the SNPs present in a conserved region of 16S rRNA gene of Bacillus species. Also, we proposed three novel Bacillus strains that produce Cry proteins and belong to B. subtilis group.

microbiology↗

bioRxiv2020

SpineS: An interactive time-series analysis software for dendritic spines

Live fluorescence imaging has shown the dynamic nature of dendritic spines, with changes in shape occurring both during development and in response to activity. The structure of a dendritic spine positively correlates with its functional efficacy. Learning and memory studies have shown that great deal of the information stored by a neuron is contained in the synapses. High precision tracking of synaptic structures can give hints about the dynamic nature of memory and help us to understand how memories evolve both in biological and artificial neural networks. Experiments that aim to investigate the dynamics behind the structural changes of dendritic spines require the collection and analysis of large time-series datasets. In this paper, we present an open-source software called SpineS for the automatic longitudinal structural analysis of dendritic spines with additional features for manual intervention to ensure optimal analysis. Our extensive experimental analyses on multiple datasets demonstrate that SpineS can achieve a high-level performance on samples collected both by two-photon and confocal imaging systems.

neuroscience↗