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Expansion and contraction of the DUP240 multigene family in Saccharomyces cerevisiae populations.

The influence of duplicated sequences on chromosomal stability is poorly understood. To characterize chromosomal rearrangements involving du … py number and sequence. We characterized DNA sequences that are likely involved in homologous or nonhomologous recombination events and are responsible for intra- and interchromosomal rearrangements that cause the creation and disappearance of DUP240 paralogs. The tandemly repeated DUP240 genes seem to be privileged sites of gene birth and death.

Distribution, cloning, characterisation and mutagenesis of sodC, the gene encoding copper/zinc superoxide dismutase, a potential determinant of virulence, in Haemophilus ducreyi.

The sodC gene encoding the periplasmic enzyme copper/zinc superoxide dismutase (CuZnSOD) has been cloned from Haemophilus ducreyi, the causative agent of the genital ulcer disease, chancroid. Examination of a collection of diverse strains indicates that it is present throughout the species. Cloned sodC has been expressed in E. coli and shown to encode active enzyme. Insertional mutagenesis was used to construct a non-functional version of the gene. This has been transferred into the chromosome of the parent H. ducreyi strain by electroporation and homologous recombination, in preparation for s…

Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor.

The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR-deficient (Ahr-/-) mouse line was constructed by homologous recombination in embryonic stem cells. Almost half of the mice died shortly after birth, whereas survivors reached maturity and were fertile. The Ahr-/- mice showed decreased accumulation of lymphocytes in the spleen and lymph nodes, but not in the thymus. The livers of Ahr-/- mice were reduced in size by 50 percent and showed bile duct fibrosis Ahr-/- mice were also nonresponsive with r…

bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine.

Transgenic mice homozygously lacking in the bcl-2 gene were generated using homologous recombination in embryonal stem cells. The complete absence of Bcl-2 alpha and -beta proteins did not interfere with normal embryonic development. Abnormalities became evident after birth, although the severity varied among homozygous null mice, bcl-2-/- mice displayed pleiotropic abnormalities similar to those in the previously described bcl-2-/- mice, including growth retardation, smaller ears, short lives, polycystic kidney, atrophic thymus and spleen with accelerated apoptotic cell death of lymphocytes, …

Targeted disruption of the neuronal nitric oxide synthase gene.

By homologous recombination, we have generated mice that lack the neuronal nitric oxide synthase (NOS) gene. Neuronal NOS expression and NADPH-diaphorase (NDP) staining are absent in the mutant mice. Very low level residual catalytic activity suggests that other enzymes in the brain may generate nitric oxide. The neurons normally expressing NOS appear intact, and the mutant NOS mice are viable, fertile, and without evident histopathological abnormalities in the central nervous system. The most evident effect of disrupting the neuronal NOS gene is the development of grossly enlarged stomachs, w…

Updates in US Food and Drug Administration approvals for poly-ADP-ribose polymerase inhibitors in Ovarian Cancer: A society of gynecologic oncology clinical practice review.

This Society of Gynecologic Oncology review synthesizes updated data from pivotal trials of poly-ADP-ribose polymerase inhibitors (PARPi) in ovarian cancer. Multiple phase III trials established PARPi as effective maintenance therapy, demonstrating substantial progression-free survival across biomarker-defined subgroups, particularly for patients with BRCA-mutated and homologous recombination-deficient (HRD) ovarian cancer. However, mature overall survival analyses and safety signals prompted the US Food and Drug Administration to narrow indications, while the broader indications were maintain…

Leveraging DNA repair deficiency to personalize radiopharmaceutical therapy in prostate cancer.

Radiopharmaceutical therapies targeting prostate-specific membrane antigen (PSMA) have transformed the management of metastatic prostate cancer, yet inter-patient variability in therapeutic response remains a critical challenge. Emerging evidence indicates that defects in DNA repair pathways, including homologous recombination deficiency (HRD) and mismatch repair deficiency (MMRd), sensitize tumor cells to ionizing radiation by impairing damage resolution. Ongoing research explores the potential of integrating genomic profiling of DNA repair defects to optimize patient selection and personaliz…

The emerging role of PARP inhibitors in prostate cancer: A narrative review.

Prostate cancer (PC) is the second most common cancer and the fifth leading cause of cancer mortality in men, worldwide. Genomic analysis identified alterations in DNA damage repair (DDR) pathways, in up to 30% of metastatic castration-resistant prostate cancer (mCRPC). Homologous recombination repair (HRR) mutations in BRCA1/2 emerged as a relevant biomarker in PC, linked to aggressive behavior, unfavorable outcomes and notable responses to poly-ADP ribose polymerase inhibitors (PARPi). While PARPi efficacy in BRCA-mutated mCRPC is well established, their role in earlier disease stages is cur…

ATR Inhibitors in Platinum-Resistant Ovarian Cancer.

Platinum-resistant ovarian cancer (PROC) is one of the deadliest types of epithelial ovarian cancer, and it is associated with a poor progno … ted attention as a promising class of targeted drugs that can regulate the cell cycle and influence homologous recombination (HR) repair. In recent years, many preclinical and clinical studies have demonstrated the efficacy of ATRis in PROC. This review focuses on the anticancer mechanism of ATRis and the progress of research on ATRis for PROC.

Молекулярные механизмы эволюции Поксвируса.

Считается, что поксивирусы развиваются относительно медленно, поскольку они являются двойными патогенами ДНК с корректирующими полимеразами. Однако оксивирусы имеют высокоприспособляемые геномы и могут претерпевать относительно быстрые генотипические и фенотипические изменения, о чем свидетельствует недавний рост передачи вируса обезьянопокс в организм человека. Достижения в технологии глубокой последовательности продемонстрировали постоянную вариацию нуклеотида у оксивирусных популяций, которая была недооценена. Появляется также понимание той роли, которую геномные архитектурные изменения игр

Совпадение в аннотации оригинала
Poxviruses are often thought to evolve relatively slowly because they are double-stranded DNA pathogens with proofreading polymerases. Howev … rchitectural changes play in shaping poxvirus evolution. These mechanisms include homologous and nonhomologous recombination, gene duplications, gene loss, and the acquisition of new genes through horizontal gene transfer. In this review, we discuss these evolutionary mechanisms and their potential roles for adaption to novel host species and modulating virulence.

Real-world genetic testing patterns in metastatic castration-resistant prostate cancer.

Aim: To assess the patterns of genetic testing for homologous recombination repair mutations in patients with metastatic castration-resistant prostate cancer (mCRPC) pre-PARP inhibitors approval. Patients & methods: mCRPC patients were selected in an oncology electronic medical records database. Patterns and predictors of testing for ATM, BRCA1/2, CDK12, PALB2 and FANCA gene alterations were assessed. Results: Of 5213 mCRPC patients, 674 (13%) had a documented genetic test. The number of tested patients increased from 1 in 2013 to 313 in 2018 (out of 3161 and 3010 clinically active patients, r…

Upregulated expression of MTFR2 as a novel biomarker predicts poor prognosis in hepatocellular carcinoma by bioinformatics analysis.

Aim: The authors investigated the clinical role of MTFR2 in hepatocellular carcinoma (HCC) progression. Results: MTFR2 expression and methylation were abnormal in HCC tissues, and HCC patients with increased MTFR2 expression or methylation had poor or better overall survival, respectively. In addition, increased MTFR2 expression was correlated with age, grade, cancer stage and T stage. MTFR2 was an independent predictor of dismal prognosis in HCC patients. MTFR2 was involved in HCC progression by modulating the cell cycle, homologous recombination, DNA replication, p53 signaling pathway, etc. …

Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors.

Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequently occurs in PFA ependymomas, suppresses homologous recombination (HR)-mediated DNA repair. Mechanistically, CXorf67 interacts with PALB2 and inhibits PALB2-BRCA2 interaction, thereby inhibiting HR repair. Concordantly, tumor cells with high CXorf67 expression levels show increas…

Contribution of VMA5 to vacuolar function, stress response, ion homeostasis and autophagy in Candida albicans.

AIM: V-ATPase is a conservative multi-subunit enzyme in eukaryotes and modulates several cellular responses. This study aimed to illustrate the roles of Vma5 in vacuolar function, oxidative stress response, calcium homeostasis, autophagy and virulence. MATERIALS & METHODS: The vma5Δ/Δ mutant was obtained using PCR-mediated homologous recombination. The functions of Vma5 were investigated by a series of biochemical and systemic infection methods. RESULTS: Disruption of VMA5 led to growth inhibition, vacuolar dysfunction, disturbance of calcium homeostasis and inhibition of calcium-related oxi…

A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.

The Ncx/Hox11L.1 gene, a member of the Hox11 homeobox gene family, is mainly expressed in neural crest-derived tissues. To elucidate the role of Ncx/Hox11L.1, the gene has been inactivated in embryonic stem cells by homologous recombination. The homozygous mutant mice were viable. These mice developed megacolon with enteric ganglia by age 3-5 wk. Histochemical analysis of the ganglia revealed that the enteric neurons hyperinnervated in the narrow segment of megacolon. Some of these neuronal cells degenerated and neuronal cell death occurred in later stages. We propose that Ncx/Hox11L.1 is requ…

An interstitial duplication of the X chromosome in a male allows physical fine mapping of probes from the Xq13-q22 region.

An insertional translocation into the proximal long arm of the X chromosome in a boy showing muscular hypotony, growth retardation, psychomotor retardation, cryptorchidism, and Pelizaeus-Merzbacher disease (PMD) was identified as a duplication of the Xq21-q22 segment by employing DNA probes. With densitometric scanning for quantitation of hybridization signals, 15 Xq probes were assigned to the duplicated region. Analysis of the duplication allowed us to dissect the X-Y homologous region physically at Xq21 and to refine the assignments of the loci for DXYS5, DXYS12, DXYS13, DXS94, DXS95, DXS96

High-resolution genomic analysis reveals abundant mosaic outcomes of bacterial natural transformation independent of MutS-mediated mismatch repair.

The nature and breadth of horizontal gene transfer outcomes specific to natural transformation remain elusive. We present a genome-scale ana … h the length of the nearest stretch of perfect homology, and these segments defy minimal, efficient homologous recombination rules. Sites of transformation and their associated intervening recipient sequences were not distinguished by overall percent identity, GC content, or median gene expression. Mismatch repair activity by MutS also failed to explain the breadth and fr …

Efficient removal of loxP-flanked DNA sequences in a gene-targeted locus by transient expression of Cre recombinase in fertilized eggs.

The bacteriophage P1 Cre/loxP site-specific recombination system is a useful tool for engineering chromosomal changes in animal cells. Transient expression of the Cre recombinase gene directly introduced into fertilized eggs by pronuclear injection has been reported to provide an efficient method of transgene modulation in fertilized eggs. In the present study, we examined the efficacy of this method to remove loxP-flanked DNA sequences in a gene-targeted locus in fertilized eggs. We replaced a part of the T-cell receptor gamma (TCR V gamma) locus with homologous sequences containing a loxP-fl

Pure duplication 21q21.2-->qter due to a rea(21) in a Down syndrome girl. Remarks on nomenclature.

We report on an 8-year-old girl with a typical Down syndrome phenotype and a 46,XX,rea(21)(qter-->p12::q21.2-->qter).ish rea(21)(qter-->pl2::q21.2-->qter)(LSI 21++,AML1++) karyotype; the mother had normal chromosomes but the father was unavailable. The great resemblance of the patient's rearranged chromosome to the rec(21)dup(q) from a parental pericentric inversion suggests that it would be better depicted as a recombinant-like chromosome. Altogether, 13 recombinant-like chromosomes of de novo or unknown (parents not karyotyped) origin have been described. Although these rearranged chromosome

[Cloning and expression of flagellin gene from a Chinese Borrelia burgdorferi PD91 strain].

OBJECTIVE: To study the cloning and expression of flagellin gene from Chinese Borrelia burgdorferi, PD91 strain and to evaluate the feasibility of using recombinant protein as diagnostic antigen when comparing the gene sequence with flagellin gene from North American Borrelia burgdorferi B31. METHODS: The piece of genes coding flagellin from Chinese Borrelia burgdorferi PD91 by polymerase chain reaction (PCR) method was obtained, and constructed recombinant plasmid, before transformed into E. coli BL21 strain, and induced. The recombinant plasmid was identified with enzyme cutoff and gene seq