Recent work has highlighted the importance of alternative, error-prone mechanisms for joining DNA double-strand breaks (DSB) in mammalian cells. These noncanonical, non-homologous end joining (NHEJ) pathways threaten genomic stability but remain poorly characterized. The RAG post-cleavage complex normally prevents V(D)J recombination-associated DSBs from accessing alternative NHEJ. Because the MRE11/RAD50/NBS1 complex localizes to RAG-mediated DSBs and possesses DNA end tethering, processing and joining activities, we asked whether it plays a role in the mechanism of alternative NHEJ, or participates in regulating access of DSBs to alternative repair pathways. We find that NBS1 is required for alternative NHEJ of hairpin coding ends, suppresses alternative NHEJ of signal ends, and promotes proper resolution of inversional recombination intermediates. These data demonstrate that the MRE11 complex functions at two distinct levels, regulating repair pathway choice (likely through enhancing the stability of DNA-end complexes) and participating in alternative NHEJ of coding ends.

No abstract

Syncope is a common presenting complaint in the emergency department, accounting for approximately 1 to 3% of presentations and up to 6% of admissions. Syncope is properly defined as a brief loss of consciousness and postural tone followed by spontaneous and complete recovery. Often syncope must be distinguished from other etiologies of transient loss of consciousness, such as seizures and hypoglycemia. Comprehension of the pathogenesis, clinical presentation, and prognosis of the varied causes of syncope is essential if emergency physicians are to succeed in identifying patients at risk for adverse events while also reducing unnecessary syncope admissions. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of syncope. Figures show heart block, prolonged QTc and torsades de pointes, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, and Brugada syndrome.  This review contains 6 figures, 18 tables, and 58 references. Keywords: Syncope, near-syncope, pre-syncope, arrhythmia, dysrhythmia, sudden cardiac death, vasovagal, passing out, neurocardiogenic

Syncope is a common presenting complaint in the emergency department, accounting for approximately 1 to 3% of presentations and up to 6% of admissions. Syncope is properly defined as a brief loss of consciousness and postural tone followed by spontaneous and complete recovery. Often syncope must be distinguished from other etiologies of transient loss of consciousness, such as seizures and hypoglycemia. Comprehension of the pathogenesis, clinical presentation, and prognosis of the varied causes of syncope is essential if emergency physicians are to succeed in identifying patients at risk for adverse events while also reducing unnecessary syncope admissions. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of syncope. Figures show heart block, prolonged QTc and torsades de pointes, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, and Brugada syndrome.  This review contains 6 figures, 15 tables, and 58 references. Keywords: Syncope, near-syncope, pre-syncope, arrhythmia, dysrhythmia, sudden cardiac death, vasovagal, passing out, neurocardiogenic