BRCA2 Regulates Transcription Elongation by RNA Polymerase II to Prevent R-Loop Accumulation.

The controlled release of RNA polymerase II (RNAPII) from promoter-proximal pausing (PPP) sites is critical for transcription elongation in metazoans. We show that the human tumor suppressor BRCA2 interacts with RNAPII to regulate PPP release, thereby preventing unscheduled RNA-DNA hybrids (R-loops) implicated in genomic instability and carcinogenesis. BRCA2 inactivation by depletion or cancer-causing mutations instigates RNAPII accumulation and R-loop accrual at PPP sites in actively transcribed genes, accompanied by γH2AX formation marking DNA breakage, which is reduced by ERCC4 endonuclease depletion.

Symmetry-related clustering of positive charges is a common mechanism for heparan sulfate binding in enteroviruses.

Coxsackievirus A9 (CAV9), a member of the Picornaviridae family, uses an RGD motif in the VP1 capsid protein to bind to integrin αvβ6 during cell entry. Here we report that two CAV9 isolates can bind to the heparan sulfate/heparin class of proteoglycans (HSPG). Sequence analysis identified an arginine (R) at position 132 in VP1 in these two isolates, rather than a threonine (T) as seen in the nonbinding strains tested.

Evolution and conservation in human parechovirus genomes.

Human parechoviruses (HPeVs) are frequent pathogens with a seroprevalence of over 90% in adults. Recent studies on these viruses have increased the number of HPeV types to eight. Here we analyse the complete genome of one clinical isolate, PicoBank/HPeV1/a, and VP1 and 3D protein sequences of PicoBank/HPeV6/a, isolated from the same individual 13 months later.

Analysis of a new human parechovirus allows the definition of parechovirus types and the identification of RNA structural domains.

Human parechoviruses (HPeV), members of the Parechovirus genus of Picornaviridae, are frequent pathogens but have been comparatively poorly studied, and little is known of their diversity, evolution, and molecular biology. To increase the amount of information available, we have analyzed 7 HPeV strains isolated in California between 1973 and 1992. We found that, on the basis of VP1 sequences, these fall into two genetic groups, one of which has not been previously observed, bringing the number of known groups to five.

Molecular analysis of an echovirus 3 strain isolated from an individual concurrently with appearance of islet cell and IA-2 autoantibodies.

Growing evidence has implicated members of the genus Enterovirus of the family Picornaviridae in the etiology of some cases of type 1 diabetes (T1D). To contribute to an understanding of the molecular determinants underlying this association, we determined the complete nucleotide sequence of a strain of echovirus 3 (E3), Human enterovirus B (HEV-B) species, isolated from an individual who soon after virus isolation developed autoantibodies characteristic of T1D. The individual has remained positive for over 6 years for tyrosine phosphatase-related IA-2 protein autoantibodies and islet cell autoantibodies, indicating an ongoing autoimmune process, although he has not yet developed clinical T1D.

Integrin alpha v beta 6 is an RGD-dependent receptor for coxsackievirus A9.

Coxsackievirus A9 (CAV9), a member of the Enterovirus genus of Picornaviridae, is a common human pathogen and is one of a significant number of viruses containing a functional arginine-glycine-aspartic acid (RGD) motif in one of their capsid proteins. Previous studies identified the RGD-recognizing integrin alpha(v)beta(3) as its cellular receptor. However, integrin alpha(v)beta(6) has been shown to be an efficient receptor for another RGD-containing picornavirus, foot-and-mouth disease virus (FMDV).