HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Regulation of DSB Repair by Cell-cycle Signaling and the DNA Damage Response

Of the many types of DNA lesions, DNA double-strand breaks (DSBs) are considered the most harmful, because one unrepaired DSB is sufficient to trigger permanent growth arrest and cell death. In addition, DSBs are potent inducers of gross chromosomal rearrangements such as deletions, translocations and amplifications. DSB signalling and repair through different pathways is crucial to preserve genomic integrity and maintain cellular homeostasis. Therefore, it is no wonder if the cell finely regulates DSB repair pathways in the different cell cycle phases and following activation of the DNA damage checkpoint. In this short essay we will illustrate some known aspects of the regulation of DSB repair in the mitotic cell cycle. In particular we will focus on the balance of the two main DSB repair pathways: NHEJ, non-homologous end joining and H(D)R, homologous (directed) recombination, as well as on the regulation of the resolution of joint molecules that arise during H(D)R