WRN interacting protein 1 (WRNIP1) was originally identified as a protein that interacts with the Werner syndrome responsible gene product (WRN). WRNIP1 is a highly conserved protein from E. coli to humans. Genetic studies in budding yeast suggested that the yeast orthlog of WRNIP1, Mgs1, may function in a DNA damage tolerance pathway that is similar to, but distinct from, the templateswitch damage avoidance pathway involving Rad6, Rad18, Rad5, Mms2, and Ubc13. Here we report that human WRNIP1 binds in an ATP dependent manner to both forked DNA that mimics stalled replication forks and to template/primer DNA. We found that WRNIP1 interacts physically with RAD18 and interferes with the binding of RAD18 to forked DNA and to template/primer DNA. In contrast, RAD18 enhances the binding of WRNIP1 to these DNAs, suggesting that WRNIP1 targets DNA bound by RAD18.

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The solitary ascidian Ascidiella aspersa (Müller, 1776) has sometimes been regarded as conspecific with A. scabra (Müller, 1776), although previous detailed morphological comparisons have indicated that the two are distinguishable by internal structures. Resolution of this taxonomic issue is important because A. aspersa has been known as a notoriously invasive ascidian, doing much damage to aquaculture e.g. in Hokkaido, Japan. We collected many specimens from European waters (including the Swedish coast, near the type localities of these two species) and Hokkaido, Japan (as an alien population) and made molecular phylogenetic analyses using the mitochondrial cytochrome c oxidase subunit I (COI) gene, and found that in terms of COI sequences all the analyzed specimens were clustered into two distinct groups, one of which is morphologically referable to A. aspersa and the other to A. scabra. Thus, these two species should be regarded as distinct from each other.

The occurrence of orange/pinkish colored lesions in the adductor muscle of Yesso scallops Patinopecten yessoensis has been known for many years in Japan; however, determination of the causative agent has not been adequately investigated. Histological examination of affected scallops in southern Hokkaido typically revealed intense host responses: hemocyte infiltration, an abundance of necrotic hemocytes, lysis of muscle fibers and in some instances melanin deposits when the lesions occurred adjacent to the shell. Microbiota analysis showed that Francisella halioticida was dominant in the lesions, and in situ hybridization using F. halioticida specific probes also confirmed the presence of this bacterium within the lesions. A F. halioticida specific PCR assay detected this bacterium in the majority of scallop lesions tested. Subsequently, three bacterial isolates were obtained from scallop lesions on modified Eugon agar supplemented with antibiotics, and these bacterial isolates were found to be F. halioticida by 16S rRNA and rpoB gene sequences. These results suggest that infection with F. halioticida is the most likely cause of the adductor muscle lesions observed in Yesso scallops. Field surveys conducted in 2017 of scallops cultured in southern Hokkaido showed that the presence of adductor muscle lesions putatively caused by F. halioticida was significantly related to mortalities and poor growth of scallops.

Minichromosome maintenance (MCM) proteins are essential factors for the prevention of the loss of extrachromosomal DNA in Saccharomyces cerevisiae [1][2][3]. A heterohexameric MCM2-7 protein complex has been identified as a component of the DNA replication licensing system that ensures a single round of DNA replication per cell cycle [4][5][6][7]. This complex functions as a replicative DNA helicase that drives the unwinding of the DNA duplex prior to semiconservative DNA synthesis at the replication forks. This notion is supported by the following findings. First, all of the MCM2-7 proteins possess DNA-dependent ATPase motifs that are common features of DNA helicases [8].Second, the MCM4/6/7 subcomplex forms the core of the MCM2-7 hexamer and exhibits intrinsic DNA helicase activity in vitro [9][10][11][12]. Third, in S. cerevisiae, MCM2-7 proteins play an essential role in both the initiation and elongation of DNA replication [13], and these proteins migrate on the genome together with the replication forks [14,15]. One of the intricacies related to the function of the MCM2-7 complex is that an isolated MCM2-7 complex does not exhibit definite DNA helicase activity in vitro, but the MCM4/6/7 hexamer does. Further, the interaction between the MCM2 protein and the MCM4/6/7 hexamer, or between the MCM3/5 proteins and the MCM4/6/7 hexamer, The antibiotic heliquinomycin, which inhibits cellular DNA replication at a half-maximal inhibitory concentration (IC 50 ) of 1.4-4 lm, was found to inhibit the DNA helicase activity of the human minichromosome maintenance (MCM) 4/6/7 complex at an IC 50 value of 2.4 lm. In contrast, 14 lm heliquinomycin did not inhibit significantly either the DNA helicase activity of the SV40 T antigen and Werner protein or the oligonucleotide displacement activity of human replication protein A. At IC 50 values of 25 and 6.5 lm, heliquinomycin inhibited the RNA priming and DNA polymerization activities, respectively, of human DNA polymerase-a/primase. Thus, of the enzymes studied, the MCM4/6/7 complex was the most sensitive to heliquinomycin; this suggests that MCM helicase is one of the main targets of heliquinomycin in vivo. It was observed that heliquinomycin did not inhibit the ATPase activity of the MCM4/6/7 complex to a great extent in the absence of single-stranded DNA. In contrast, heliquinomycin at an IC 50 value of 5.2 lm inhibited the ATPase activity of the MCM4/6/7 complex in the presence of single-stranded DNA. This suggests that heliquinomycin interferes with the interaction of the MCM4/6/7 complex with single-stranded DNA.Abbreviations BrdU, bromodeoxyuridine; FITC, fluorescein isothiocyanate; IC 50, half-maximal inhibitory concentration; MCM, minichromosome maintenance; RPA, replication protein A.