A Human BRCA2 Complex Containing a Structural DNA Binding Component Influences Cell Cycle Progression

AbstractGermline mutations of the human BRCA2 gene confer susceptibility to breast cancer. Although the function of the BRCA2 protein remains to be determined, murine cells homozygous for BRCA2 inactivation display chromosomal aberrations. We have isolated a 2 MDa BRCA2-containing complex and identified a structural DNA binding component, designated as BR CA2-A ssociated F actor 35 (BRAF35). BRAF35 contains a nonspecific DNA binding HMG domain and a kinesin-like coiled coil domain. Similar to BRCA2, BRAF35 mRNA expression levels in mouse embryos are highest in proliferating tissues with high mitotic index. Strikingly, nuclear staining revealed a close association of BRAF35/BRCA2 complex with condensed chromatin coincident with histone H3 phosphorylation. Importantly, antibody microinjection experiments suggest a role for BRCA2/BRAF35 complex in modulation of cell cycle progression

Understanding the Role of Hyponitrite in Nitric Oxide Reduction

Herein, we review the preparation and coordination chemistry of cis and trans isomers of hyponitrite, [N2O2](2-). Hyponitrite is known to bind to metals via a variety of bonding modes. In fact, at least eight different bonding modes have been observed, which is remarkable for such a simple ligand. More importantly, it is apparent that the cis isomer of hyponitrite is more reactive than the trans isomer because the barrier of N2O elimination from cis-hyponitrite is lower than that of trans-hyponitrite. This observation may have important mechanistic implications for both heterogeneous NOx reduction catalysts and NO reductase. However, our understanding of the hyponitrite ligand has been limited by the lack of a general route to this fragment, and most instances of its formation have been serendipitous

Transesophageal electrocardiography before and after intervention in atrio-ventricular nodal reentrant tachycardia

Aim. To study diagnostic value of transoesophageal electrocardiography (TE ECG) in verifying double physiology of atrio-ventricular (AV) node in differential diagnostics of supraventricular tachycardias (SVT), as well as in assessment of short and long-term treatment results in paroxysmal AV nodal reentrant tachycardia (PAVNRT).Material and methods. The study included 32 patients with PAVNRT diagnosis, verified by TE ECG. At Stage I, PAVNRT patients were clinically examined. Then intracardiac (IC) ECG and radioablation (RA) were performed at a Cardiosurgery department. At Stage II, all participants underwent TE ECG, to assess RA effectiveness 1 and 3 months later.Results. At Stage I, TE ECG demonstrated some specific features of AV node physiology. Their impact on treatment effectiveness and post-intervention clinical course was assessed at Stage II. PAVNRT in combination with impaired AV conductivity and increased effective refractory periods (EFP) of beta-pathway (>500 ms) were not contraindicative to RA of slow AV node pathways. Among these patients, AV conductivity was satisfactory, with no clinical symptoms or signs. During TE ECG, PAVNRT was difficult to diagnose in patients without double AV node conductivity and wide QRS tachycardia.Conclusion. The results obtained confirmed the importance of ТЕ ECG in PAVNRT diagnostics. RA is needed in patients with confirmed diagnosis and double AV node physiology. This method is important for identifying indications and counter-indications for intervention, for predicting complications and adverse events during RA

BRCA1 Is Associated with a Human SWI/SNF-Related Complex: Linking Chromatin Remodeling to Breast Cancer

Germline mutations in the tumor suppressor gene, BRCA1, predispose individuals to breast and ovarian cancers. Using a combination of affinity- and conventional chromatographic techniques, we have isolated a predominant form of a multiprotein BRCA1-containing complex from human cells displaying chromatin-remodeling activity. Mass spectrometric sequencing of components of this complex indicated that BRCA1 is associated with a SWI/SNF-related complex. We show that BRCA1 can directly interact with the BRG1 subunit of the SWI/SNF complex. Moreover, p53-mediated stimulation of transcription by BRCA1 was completely abrogated by either a dominant-negative mutant of BRG1 or the cancer-causing deletion in exon 11 of BRCA1. These findings reveal a direct function for BRCA1 in transcriptional control through modulation of chromatin structure