A COG in the retrograde transport machinery

PARP retains Ku at double-strand breaks C outo et al. describe how a poly ADP-ribose polymerase (PARP) helps repair DNA double-strand breaks (DSBs) by promoting the accumulation of a key protein required for nonhomologous end joining (NHEJ). PARPs are activated by DNA damage, catalyzing the poly ADP-ribosylation (PARylation) of proteins at both single-strand breaks and DSBs. In vertebrate cells, PARP1 and PARP2 regulate the repair of single-strand lesions and promote DSB repair by homologous recombination. But how PARylation promotes DSB repair by the NHEJ pathway—and which PARP is responsible— is unclear. Couto et al. investigated the functions of PARPs in Dictyostelium, a genetically tractable organism that expresses many DNA-repair proteins found in vertebrates but not lower organisms such as yeast. Couto et al. discovered that two Dictyostelium PARPs, Adprt1b and Adprt2, were required to repair single-strand DNA lesions. PARylation at DSBs, however, was principally carried out by a third PARP, Adprt1a. The NHEJ pathway was less active in Dictyostelia lacking Adprt1a because the Ku complex, which recognizes DNA ends and recruits the NHEJ repair machinery, no longer accumulated on chromatin after DNA damage. The Ku70 subunit contains a motif that binds to poly ADP-ribose. A version of Ku70 lacking this domain failed to accumulate on DNA after DSB induction and was unable to rescue the NHEJ defects of cells lacking wild-type Ku70. Senior author Nicholas Lakin now wants to identify which proteins are PARylated by Adprt1a in order to recruit or retain Ku70 at DSBs. M uslimov et al. reveal how noncanonical structural motifs target RNAs to neuronal den-drites and describe how this might go awry in a neuro-degenerative disease. Many neuronal RNAs are delivered to specifi c locations within the nerve cell. This targeting is governed by RNA-binding proteins that often recognize the three-dimensional structure of the RNA rather than its specifi c nucleotide sequence. RNA structures are complex, in part because ribonucleotides aren't restricted to forming the standard " Watson-Crick " base pairs found in DNA. Noncanonical pairing between the purine bases guanine and adenine, for example, helps to form a stem-loop structure in BC1 that targets this regulatory RNA to neuronal dendrites. Muslimov et al. found that these noncanonical base pairs were essential for the interaction of BC1 with the RNA-targeting protein hnRNP A2 and that this interaction was required for BC1's delivery to dendrites. mRNA encoding the protein kinase PKM␨ relied on a similar interaction for …