Persistent double strand break accumulation does not precede cell death in an Olaparib-sensitive BRCA-deficient colorectal cancer cell model
Abstract The poly (adenosine diphosphate (ADP)-ribosyl) polymerase inhibitors (PARPi) selectively kill cancer cells with BRCA1 or BRCA2 (BRCA)-mutations. It has been proposed that cell death induction after PARPi depends on unrepaired double strand breaks (DSBs) that accumulate due to the homologous recombination deficiency of BRCA-mutated cells. Such accumulation of DSBs is inferred mainly from the high levels of DNA damage markers like phosphorylated histone H2AX. Herein, we developed a model of isogenic cell lines to show that depletion of BRCA causes PARPi-triggered cell death, replication stress (phosphorylated-H2AX a...
Source: Genetics and Molecular Biology - December 14, 2019 Category: Genetics & Stem Cells Source Type: research
From yeast to humans: Understanding the biology of DNA Damage Response (DDR) kinases
Abstract The DNA Damage Response (DDR) is a complex network of biological processes that protect cells from accumulating aberrant DNA structures, thereby maintaining genomic stability and, as a consequence, preventing the development of cancer and other diseases. The DDR pathway is coordinated by a signaling cascade mediated by the PI3K-like kinases (PIKK) ATM and ATR and by their downstream kinases CHK2 and CHK1, respectively. Together, these kinases regulate several aspects of the cellular program in response to genomic stress. Much of our understanding of these kinases came from studies performed in the 1990s using yeas...
Source: Genetics and Molecular Biology - December 14, 2019 Category: Genetics & Stem Cells Source Type: research
DNA replication stress: oncogenes in the spotlight
Abstract Precise replication of genetic material is essential to maintain genome stability. DNA replication is a tightly regulated process that ensues faithful copies of DNA molecules to daughter cells during each cell cycle. Perturbation of DNA replication may compromise the transmission of genetic information, leading to DNA damage, mutations, and chromosomal rearrangements. DNA replication stress, also referred to as DNA replicative stress, is defined as the slowing or stalling of replication fork progression during DNA synthesis as a result of different insults. Oncogene activation, one hallmark of cancer, is able to d...
Source: Genetics and Molecular Biology - December 14, 2019 Category: Genetics & Stem Cells Source Type: research
Araucaria angustifolia chloroplast genome sequence and its relation to other Araucariaceae
Abstract Araucaria angustifolia is endemic to southern Brazil. Known as Brazilian pine, A. angustifolia is the only native conifer species with economic and social relevance in this country. Due to massive exploitation, it has suffered a significant population decline and currently is classified as critically endangered. This encouraged the scientific community to investigate genetic features in Brazilian pine to increase resources for management and preservation. In this work, RNA-Seq data was used to determine the complete nucleotide sequence of the A. angustifolia chloroplast genome (cpDNA). The cpDNA is 146,203 bp in l...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
The perturbed expression of m6A in parthenogenetic mouse embryos
Abstract Parthenogenetically activated oocytes cannot develop to term in mammals owing to abnormal epigenetic modifications. Methylation of the N6 position of adenosine (m6A) is a post-transcriptional epigenetic modification of RNA. To investigate the role of m6A methylation in parthenogenetic (PA) embryonic development, we analyzed METTL3, METTL14, FTO, ALKBH5, YTHDF2, IGF2BP1, and IGF2BP2 expression by quantitative real-time PCR. These genes were found dynamically expressed during the 2-cell, 4-cell, 8-cell, and blastocyst stages of the embryo. Compared to normally fertilized embryos, the expression of these genes was pe...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Gene pool sharing and genetic bottleneck effects in subpopulations of Eschweilera ovata (Cambess.) Mart. ex Miers (Lecythidaceae) in the Atlantic Forest of southern Bahia, Brazil
This study was conducted to investigate the genetic variability and gene pool sharing of Eschweilera ovata in five forest remnants in southern Bahia, Brazil using nuclear simple sequence repeat (nSSR) and plastid simple sequence repeat (cpSSR) microsatellite markers. cpSSR marker analysis revealed the domains of four haplotypes, showing that 80% of the individuals had only four maternal origins, reflecting a founder effect and/or genetic bottleneck. The results of cpSSR and nSSR analyses indicated moderate genetic diversity, particularly in conservation units with full protection, which showed the best parameters of all ar...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Protective effects of bark ethanolic extract from Spondias dulcis Forst F. against DNA damage induced by benzo[a]pyrene and cyclophosphamide
This study evaluated the genotoxicity, mutagenicity, antigenotoxicity, and antimutagenicity effects on biochemical parameters of oxidative stress of the Spondias dulcis bark ethanolic extract on mice. The extract was evaluated in the doses of 500, 1000, and 1500 mg/kg bw via gavage. To evaluate the protective effects of the extract, benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) were chosen as DNA damage inducers. Genotoxicity and antigenotoxicity were evaluated by the comet assay. Cytotoxicity, mutagenicity, and antimutagenicity were evaluated by the micronucleus test in bone marrow and peripheral blood. The biochemical...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Chromosomal variability in Brazilian species of Anthurium Schott (Araceae): Heterochromatin, polyploidy, and B chromosomes
Abstract The genus Anthurium has a Neotropical distribution, with karyotype predominance of x = 15, although some species show disploidy or polyploid variations. The karyotypes of seven species and different populations of Anthurium were analyzed using fluorochrome CMA and DAPI staining. The karyotypes were composed of meta- and submetacentric chromosomes, with numbers varying from 2n = 30 to 2n = 60. Supernumerary euchromatic chromosomes were observed in A. affine, and supernumerary heterochromatic chromosomes were observed in A. gladiifolium and A. petrophilum. Polyploidy was recurrent in the Anthurium species analyzed, ...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Ammopiptanthus mongolicus stress-responsive NAC gene enhances the tolerance of transgenic Arabidopsis thaliana to drought and cold stresses
Abstract Drought and cold are the primary factors limiting plant growth worldwide. The Ammopiptanthus mongolicus NAC11 (AmNAC11) gene encodes a stress-responsive transcription factor. Expression of the AmNAC11 gene was induced by drought, cold and high salinity. The AmNAC11 protein was localized in the nucleus and plays an important role in tolerance to drought, cold and salt stresses. We also found that differential expression of AmNAC11 was induced in the early stages of seed germination and was related to root growth. When the AmNAC11 gene was introduced into Arabidopsis thaliana by an Agrobacterium-mediated method, the...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Genome-wide identification and characterization of R2R3-MYB genes in Medicago truncatula
In this study, we used RNA-seq data to analyze and identify R2R3-MYB genes in the genome of Medicago truncatula. Phylogenetic analysis classified 150 MtMYB genes into 21 subfamilies with homologs. Out of the 150 MtMYB genes, 139 were distributed among 8 chromosomes, with tandem duplications (TD) and segment duplications (SD). Microarray data were used for functional analysis of the MtMYB genes during growth and developmental processes providing evidence for a role in tissues differentiation, seed development processes, and especially the nodulation process. Furthermore, we investigated the expression of MtMYB genes in resp...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Mapping of QTL for total spikelet number per spike on chromosome 2D in wheat using a high-density genetic map
In this study, we evaluated 138 F8 recombinant inbred lines (RILs) derived from an F2 population of a synthetic hexaploid wheat line (SHW-L1) and a common wheat cultivar (Chuanmai 32) for TSS in six different environments. To identify quantitative trait loci (QTL) for TSS, we constructed an integrated high-density genetic map of chr. 2D containing two simple sequence repeats, 35 diversity array technology markers, and 143 single nucleotide polymorphisms. We identified three stable QTL for TSS that individually explained 9.7 – 19.2% of the phenotypic variation and predicted 23 putative candidate genes within the QTL mappi...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Whole genome SNPs discovery in Nero Siciliano pig
This study represents a first step in the genetic characterization of Nero Siciliano pig and also provides a platform for future comparative studies between this and other swine breeds. (Source: Genetics and Molecular Biology)
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Chromosomal characterization of Amazonian freshwater stingrays with evidence for new karyomorphs and XX/XY sex chromosomes
Abstract Cytogenetic studies in the subfamily Potamotrygoninae have provided valuable insights into the understanding of the evolution and diversification of its species. In the present study, the chromosomal features of seven nominal potamotrygonin species are provided: Plesiotrygon iwamae (2n=74, FN=120), Potamotrygon amazona (2n=66, FN=107), P. constellata (2n=66, FN=110), P. leopoldi (2n=64, FN=102), P. motoro (2n=66, FN=106) from four different localities, and P. orbignyi (2n=66, FN=106), P. scobina (2n=66, FN=104), from Central Amazon. Additionally, we found a new karyomorph in P. wallacei. We considered the localiza...
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Perforin gene PRF1 c.900C> T polymorphism and HIV-1 vertical transmission
This study aims at evaluating the role of the c.900C> T PRF1 gene (encoding for perforin-1) polymorphism (rs885822) in HIV-1 MTCT. The PRF1 c.900C> T polymorphism was genotyped in 331 children from Zambia using a Taqman probe on a Real Time PCR platform. The PRF1 c.900C> T C/T genotype was more frequent among HIV-1 exposed but non-infected children than in HIV-1 positive cases, and the results were confirmed among children infected during breastfeeding. PRF1 c.900C> T correlated with protection against HIV-1 MTCT, suggesting its role in HIV-1 vertical transmission. (Source: Genetics and Molecular Biology)
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
Humoral immune response in adult Brazilian patients with Mucolipidosis III gamma
Abstract Mucolipidosis II and III (ML II and III) alpha/beta and ML III gamma are lysosomal diseases caused by GlcNAc-1-phosphotransferase deficiency. Previous data indicate that MLII patients have functionally impaired immune system that contributes to predisposition to infections.We evaluated the immunological phenotype of three Brazilian patients with ML III gamma. Our data suggest that the residual activity of GlcNAc-1-phosphotransferase in patients with ML III gamma is enough to allow the targeting of the lysosomal enzymes required for B-cell functions maintenance. (Source: Genetics and Molecular Biology)
Source: Genetics and Molecular Biology - November 14, 2019 Category: Genetics & Stem Cells Source Type: research
