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Genomic Instability (2):
Recent article
Genomic Instability
Abstract
Attempts to determine the clinical significance of BRCA1/2 mutations in ovarian cancer have produced conflicting results.
To determine the relationships between BRCA1/2 deficiency (ie, mutation and promoter hypermethylation) and overall survival (OS), progression-free...
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PMID: 21990299
PDF is available here.
PDF is available here.
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Abstract
We examined the effects of aneuploidy on genomic stability. We analyzed 13 budding yeast strains that carry extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. Most strains displayed increased chromosome loss and mitotic recombi...
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PMID: 21852501
PDF is available here.
PDF is available here.
Mutation Research (713)1-2 2011
Abstract
We show that hESC demonstrate high levels of endogenous reactive oxygen species (ROS) which can contribute to DNA damage and may arise from high levels of metabolic activity. To potentially counter genomic instability caused by DNA damage, we find that hESC employ two strategies: First, these cells...
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PMID: 21718709
PDF is available here.
PDF is available here.
PLoS Genetics (7)6 2011
Abstract
We show that untimely activation of replication origins during the G1 phase is genotoxic and induces genomic instability in the budding yeast Saccharomyces cerevisiae. Our data indicate that cells preserve a low level of the initiation factor Sld2 to prevent untimely initiation during the normal cel...
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PMID: 21698130
PDF is available here.
PDF is available here.
Cancer Cell (19)5 2011
Abstract
We show that mice lacking the ATM cofactor ATMIN in B cells (ATMIN(ΔB/ΔB)) have impaired ATM signaling and develop B cell lymphomas. Notably, ATMIN(ΔB/ΔB) cells exhibited defective peripheral V(D)J rearrangement and CSR, resulting in translocations involving the Igh and Igl loci, indicating that...
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PMID: 21575860
PDF is available here.
PDF is available here.
DNA Repair (10)5 2011
Abstract
We demonstrate that 2-5 base pair deletion mutagenesis also strongly increases in rnh201Δ strains encoding wild type DNA polymerases. As in the pol2-M644G strains, the deletions occur at repetitive sequences and are orientation-dependent, suggesting that mismatches involving misaligned strands aris...
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PMID: 21414850
PDF is available here.
PDF is available here.
Abstract
Estrogen receptor (ER) remains one of the most important biomarkers for breast cancer subtyping and prognosis, and comparative genome hybridization has greatly contributed to the understanding of global genetic imbalance. The authors used single-nucleotide polymorphism (SNP) arrays to compare overall...
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PMID: 21523713
PDF is available here.
PDF is available here.
Cell Cycle (10)8 2011
Abstract
We show that RNF8 and RNF168 are recruited to DNA damage foci in late mitosis, presumably to prime sites for 53BP1 recruitment in early G1. Interestingly, we show that, although RNF8, RNF168 and 53BP1 are excluded from DSB sites during most of mitosis, they associate with mitotic structures such as...
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PMID: 21412056
PDF is available here.
PDF is available here.
New England Journal of Medicine (364)13 2011
Abstract
Abstract
The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading...
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PMID: 21376230
PDF is available here.
PDF is available here.
Mutation Research (711)1-2 2011
Abstract
We review the current state of knowledge on the role of ROS-induced oxidative stress in altering the genetic and epigenetic involvement during human carcinogenesis....
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PMID: 21419141
PDF is available here.
PDF is available here.
Cell Cycle (10)4 2011
Abstract
We report, that Chk1 co-localized with the nucleolar marker, fibrillarin in response to radiation-induced DNA damage in human cells. Interestingly, in vitro studies using GST pull down assays identified the dual-specificity serine/threonine nucleolar phosphatase Cdc14B as a Chk1 substrate. Furthermo...
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PMID: 21301228
PDF is available here.
PDF is available here.
Abstract
We critically evaluate whether measurements of telomere lengths and telomerase levels may be clinically utilized as diagnostic markers in solid tumors, with emphasis on breast and prostate cancer as representative examples. Future directions focusing on the direct detection of dysfunctional telomere...
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PMID: 21352473
PDF is available here.
PDF is available here.
Abstract
Genomic instability refers to an increased tendency of alterations in the genome during the life cycle of cells. It is a major driving force for tumorigenesis. During a cell division, genomic instability is minimized by four major mechanisms: high-fidelity DNA replication in S-phase,...
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PMID: 21278445
PDF is available here.
PDF is available here.
Abstract
We summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma....
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PMID: 21253387
PDF is available here.
PDF is available here.
Abstract
We show that yeast INO80 facilitates these diverse processes at least in part by controlling genome-wide distribution of the histone variant H2A.Z. In the absence of INO80, H2A.Z nucleosomes are mislocalized, and H2A.Z levels at promoters show reduced responsiveness to transcriptional changes, sugge...
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PMID: 21241891
PDF is available here.
PDF is available here.
Fortschritte der Arzneimittelforschung. Progress in drug research. Progres des recherches pharmaceutiques (67) 2011
Abstract
The successful establishment and stable maintenance of cell identity are critical for organismal development and tissue homeostasis. Cell identity is provided by epigenetic mechanisms that facilitate a selective readout of the genome. Operating at the level of chromatin, they establish defined gene...
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PMID: 21141724
PDF is available here.
PDF is available here.
Abstract
We provide a description of the actual stage of knowledge of the nuclear structure of Trypanosoma cruzi. As an early divergent eukaryote, it presents unique and/or reduced events of DNA replication, transcription and repair as well as RNA processing and transport to the cytosol. Nevertheless, it sho...
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PMID: 21820560
PDF is available here.
PDF is available here.
Fortschritte der Arzneimittelforschung. Progress in drug research. Progres des recherches pharmaceutiques (67) 2011
Abstract
We will briefly summarize our current knowledge of the epigenetic patterns and mechanisms of gene regulation in healthy tissues and relate this to what is known for cancer genomes. Our focus will be on DNA methylation. We will review the current standing of technologies that have been developed over...
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PMID: 21141723
PDF is available here.
PDF is available here.
Abstract
We focus on one of the most important mechanisms underpinning tumor robustness and degeneracy, the cellular heterogeneity that is the hallmark of most solid tumors. Based on a combination of computational, experimental and clinical studies we argue that stochastic noise is an underlying cause of tum...
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PMID: 20944865
PDF is available here.
PDF is available here.
Abstract
Genome variability and changes in immune homeostasis, induced in man in the course of long-term industrial contact with ionizing radiation (IR) sources were studied by using unique biomaterials stored in the Radiobiological Repository for Human Tissues at the Southern Urals Biophysics Institute, FMBA...
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PMID: 21520613
PDF is available here.
PDF is available here.
Voprosy Virusologii (56)1 2011
Abstract
The review characterizes the currently used cold-adapted donor strains of influenza virus attenuation to prepare cold-adapted reassortants with actual epidemic influenza virus strains. It considers new procedures for preparing attenuated influenza virus strains for live influenza vaccines, as well as...
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PMID: 21427948
PDF is available here.
PDF is available here.
EMBO Journal (29)24 2010
Abstract
We analysed the function of DCAFs and Cul4-linked proteins, and identified specific subsets required for progression through G1 and S phase. We discovered C6orf167/Mms22-like protein (Mms22L) as a putative human orthologue of budding yeast Mms22, which, together with cullin Rtt101, regulates genome...
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PMID: 21113133
PDF is available here.
PDF is available here.
DNA Repair (9)12 2010
Abstract
The repair of DNA double strand breaks (dsb) is important for maintaining the physical and genetic integrity of the genome. Moreover, in humans it is associated with the prevention of diseases such as immune deficiencies and cancer. This review briefly explores the fundamental strate...
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PMID: 21115283
PDF is available here.
PDF is available here.
Abstract
We show that BRCA2 associates with telomeres during the S and G2 phases of the cell cycle and facilitates the loading of RAD51 onto telomeres. Conditional deletion of Brca2 and inhibition of Rad51 in mouse embryonic fibroblasts (MEFs), but not inactivation of Brca1, led to shortening of telomeres an...
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PMID: 21076401
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)45 2010
Abstract
We tested whether chromatin modifications affected the requirement for Rtt107 and Slx4 during DNA damage repair. Here, we report that the sensitivity to DNA-damaging agents of rtt107Δ and slx4Δ mutants was rescued by inactivation of the chromatin regulatory pathway leading to H3 K79 trimethylation...
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PMID: 20810656
PDF is available here.
PDF is available here.
Bulletin du cancer (97)11 2010
Abstract
We are presently facing lists comprising several hundreds of genes. These correspond to genes affected by structural rearrangements or mutations, those modified at the epigenetic level and, more recently, miRNAs. The current challenge resulting from this brutal increase will be to sort out founder f...
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PMID: 21059490
PDF is available here.
PDF is available here.
Bulletin du cancer (97)11 2010
Abstract
Genomic DNA displays a non canonical structure prone to be damaged and modified by genotoxic stresses, which are induced either by the endogenous metabolism or attacks from environment or therapeutic pressure. Several molecular pathways allow cells to repair such DNA lesions. Additional mechanisms h...
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PMID: 21084240
PDF is available here.
PDF is available here.
Abstract
Abstract
We harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregul...
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PMID: 20981101
PDF is available here.
PDF is available here.
Cell Cycle (9)21 2010
Abstract
We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building bloc...
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PMID: 21051947
PDF is available here.
PDF is available here.
Abstract
We show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Metastatic mouse and human tumours deficient in TAp63 express Dicer at very low levels, and we found that modulation of expression of Dicer and miR-...
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PMID: 20962848
PDF is available here.
PDF is available here.
Cell Cycle (9)20 2010
Abstract
We have recently demonstrated that histone protein levels are regulated posttranslationally by the DNA damage checkpoint kinase Rad53 and ubiquitin-proteasome dependent proteolysis in the budding yeast. However, the underlying mechanism/s via which excess histones exert their deleterious effects in...
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PMID: 20948314
PDF is available here.
PDF is available here.
Genetika (Moskva) (46)10 2010
Abstract
Chromosomal novelties and the level of meiotic and mitotic abnormalities were studied in a hybrid zone between two chromosomally differentiated Spalax cytotypes of 2n = 58 and 2n = 52. These cytotypes differ by five Rb fusions, four centromeric shifts accompanied by heterochromatin deletion, one par...
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PMID: 21250542
PDF is available here.
PDF is available here.
Abstract
p53 regulates the cell cycle and DNA repair pathways as part of its unequivocally important function to maintain genomic stability. Intriguingly, recent studies show that p53 can also transactivate genes involved in coordinating the two major pathways of energy generation to promote...
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PMID: 20919942
PDF is available here.
PDF is available here.
Abstract
We have discussed how p53 could play a role in preventing potentially harmful oxidative state and cell proliferation by pro-oncogenic pathways such as PI3K/AKT/mTOR and WNT/β-catenin or under hypoxia state. In addition, we have considered potential mechanisms by which p53 could collaborate wi...
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PMID: 20919943
PDF is available here.
PDF is available here.
Current Drug Targets (11)10 2010
Abstract
One of the main reasons why most patients with advanced cancer are not curable with the therapies available is the broad heterogeneity of cancer cells, inherently related to their genomic instability that reflects defects of cell cycle checkpoints and DNA mismatch repair (MMR). The present paper rev...
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PMID: 20840074
PDF is available here.
PDF is available here.
Discovery medicine (10)53 2010
Abstract
Repetitive DNA sequences constitute a large fraction of the genomes of humans and other animal species. Tandem repeats are a major class of repetitive DNA and the extent of their polymorphic distributions and functions within the human genome are only beginning to be explored. Tandem repeat polymorp...
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PMID: 21034672
PDF is available here.
PDF is available here.
Abstract
Gastrointestinal stromal tumors (GISTs) historically were grouped with leiomyosarcomas (LMSs) based on their morphologic similarities; however, recently, GIST was established unequivocally as a distinct type of sarcoma based on its molecular features and response to imatinib treatment.
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PMID: 20818650
PDF is available here.
PDF is available here.
Abstract
Cells devote a significant amount of metabolism to maintaining the stability of their genome and to preventing inappropriate chromosomal rearrangements that are characteristic of many cancers. A simple genetic assay using haploid derivatives of the yeast Saccharomyces cerevisiae provides a means to...
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PMID: 20810639
PDF is available here.
PDF is available here.
Genes & Development (24)16 2010
Abstract
We discuss the recent progress in the study of the FA pathway, such as the identification of new FANCM-binding partners and the identification of RAD51C and FAN1 (Fanconi-associated nuclease 1) as new FA pathway-related proteins. We also focus on the role of the FA pathway as a potential regulator o...
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PMID: 20713514
PDF is available here.
PDF is available here.
Epigenetics (5)6 2010
Abstract
Regulation of Set1-COMPASS-mediated H3K4 methylation and Dot1-mediated H3K79 methylation by H2BK123 ubiquitination (H2Bub1) is an evolutionarily conserved trans-histone crosstalk mechanism. How H2Bub1 impacts chromatin structure and affects Set1-COMPASS/Dot1 functions has not been fu...
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PMID: 20523115
PDF is available here.
PDF is available here.
Abstract
We investigated the role of ATM and its downstream targets in the cell-cycle control of V(D)J recombination in vivo. Our results revealed the persistence of double-strand breaks (DSBs) throughout the cell cycle in ATM(-/-) and p53(-/-) thymocytes, but the cell-cycle regulation of a V(D)J recombinase...
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PMID: 19915617
PDF is available here.
PDF is available here.
Abstract
Abstract
We study the potential of maintaining genetic variation in a two-deme model with deme-independent degree of intermediate dominance, which includes absence of G x E interaction as a special case. We present a thorough numerical analysis of a two-deme three-allele model, which allows us to identify do...
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PMID: 20363239
PDF is available here.
PDF is available here.
Abstract
We explore here the effects of distributed development on the stability of these systems, for a random parasitism model incorporating an invulnerable host stage, and a negative binomial model that displays generation cycles. A shifted gamma distribution was used to model the distribution of developm...
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PMID: 20380844
PDF is available here.
PDF is available here.
Abstract
Gene vectors with an untargeted insertion profile have been explored in preclinical models and clinical trials for the transfer of potentially therapeutic genetic information into somatic cells that have a high replicative potential. The gene-modified cell population can be viewed as a genetic mosai...
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PMID: 20600920
PDF is available here.
PDF is available here.
Abstract
Giant endopolyploid nuclei (>16n) can spontaneously fragment by endomitosis (nuclear internal division) into near-diploid cells with reproductive capacity (depolyploidization), and endotetra/octopolyploidy can undergo chromosome-visible meiotic-like genome reductional divisions also to replicative s...
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PMID: 20441563
PDF is available here.
PDF is available here.
Abstract
The risk associated with space radiation exposure is unique from terrestrial radiation exposures due to differences in radiation quality, including linear energy transfer (LET). Both high- and low-LET radiations are capable of inducing genomic instability in mammalian cells, and this instability is...
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PMID: 20035342
PDF is available here.
PDF is available here.
Abstract
Our results showed differential expression of neurotrophin and their associated receptor genes within 1 week after sSPE exposure. Progressive changes in the profile of expressed genes known to be involved in neurogenic signaling pathways were dependent on the sSPE dose. Our results to date suggest t...
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PMID: 20473680
PDF is available here.
PDF is available here.
Abstract
In bacteria, PriA protein, a conserved DEXH-type DNA helicase, plays a central role in replication restart at stalled replication forks. Its unique DNA-binding property allows it to recognize and stabilize stalled forks and the structures derived from them. Cells must cope with fork stalls caused by...
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PMID: 20658707
PDF is available here.
PDF is available here.
Nutrition and Cancer (62)6 2010
Abstract
We show, for the first time, that hydrophobic bile acids cause aberrations of the mitotic machinery of colon cells that can give rise to aneuploidy, the chromosomal perturbations common in colon tumors. First, we show that DOC induces a statistically significant fourfold increase in the number of mi...
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PMID: 20661832
PDF is available here.
PDF is available here.
Molecular Cell (39)2 2010
Abstract
We investigate telomere fusions caused by overexpression of mutant telomerases that add mutated telomeric repeats, thereby compromising shelterin binding to telomeric termini. While all mutant telomeric sequences tested induced heterodicentric chromosome fusions in ATM-competent cells, only those mu...
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PMID: 20670897
PDF is available here.
PDF is available here.
Nature Reviews: Cancer (10)8 2010
Abstract
An association between human papillomavirus (HPV) infection and the development of cervical cancer was initially reported over 30 years ago, and today there is overwhelming evidence that certain subtypes of HPV are the causative agents of these malignancies. The p53 and retinoblastoma proteins are w...
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PMID: 20592731
PDF is available here.
PDF is available here.
Biochemical Journal (429)2 2010
Abstract
We discuss the biological and the biochemical properties of these proteins that indicate that they play a central and important role in eukaryotic cell biology....
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PMID: 20578993
PDF is available here.
PDF is available here.
Abstract
We demonstrate that short truncations at the 5' end of a model Tomato bushy stunt virus (TBSV) RNA could be repaired during replication in yeast and plant cells. Although the truncations led to the loss of important cis-regulatory elements, the genome repair mechanisms led to the recovery of promote...
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PMID: 20537671
PDF is available here.
PDF is available here.
Virus Research (151)1 2010
Abstract
Enzootic nasal tumor virus (ENTV) is a betaretrovirus of sheep (ENTV-1) and goats (ENTV-2) associated with neoplastic transformation of epithelial cells of the ethmoid turbinate. Confirmation of the role of ENTV in the pathogenesis of enzootic nasal adenocarcinoma (ENA) has yet to be resolved due to...
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PMID: 20398709
PDF is available here.
PDF is available here.
EMBO Journal (29)13 2010
Abstract
We showed that TIP5 not only mediates the establishment of rDNA silencing but also the formation of perinucleolar heterochromatin that contains centric and pericentric repeats. Our data indicated that the TIP5-mediated heterochromatin is indispensable for stability of silent rRNA genes and of major...
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PMID: 20168299
PDF is available here.
PDF is available here.
Cytogenetic and Genome Research (129)1-3 2010
Abstract
Interspecific hybrids between the related wild barley species Hordeum marinum and H. bulbosum were generated and tested regarding their chromosomal stability and chromatin properties. Unlike in H. vulgare x H. bulbosum hybrid embryos, there was no effect of temperature on uniparental chromosome elim...
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PMID: 20551604
PDF is available here.
PDF is available here.
PLoS Genetics (6)7 2010
Abstract
We use ChIP-on-chip analysis to map genomic loci decorated by phosphorylated histone H2A (gammaH2A), a Rad3 substrate that establishes a chromatin-based recruitment platform for Crb2 and Brc1 DNA repair/checkpoint proteins. Unexpectedly, gammaH2A marks a diverse array of genomic features during S-ph...
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PMID: 20661445
PDF is available here.
PDF is available here.