The eukaryotic helicase is an 11-subunit machine containing an Mcm2-7 motor ring that encircles DNA, Cdc45 and the GINS tetramer, referred to as CMG. CMG is “built” on DNA at origins in two steps. First, two Mcm2-7 rings are assembled around duplex DNA at origins in G1 phase, forming the Mcm2-7 “double hexamer.” In a second step, in S phase Cdc45 and GINS are assembled onto each Mcm2-7 ring, hence producing two CMGs that ultimately form two replication forks that travel (...) in opposite directions. Here, we review recent findings about CMG structure and function. The CMG unwinds the parental duplex and is also the organizing center of the replisome: it binds DNA polymerases and other factors. EM studies reveal a 20-subunit core replisome with the leading Pol ϵ and lagging Pol α-primase on opposite faces of CMG, forming a fundamentally asymmetric architecture. Structural studies of CMG at a replication fork reveal unexpected details of how CMG engages the DNA fork. The structures of CMG and the Mcm2-7 double hexamer on DNA suggest a completely unanticipated process for formation of bidirectional replication forks at origins. Here, we review the structure and function of CMG, the 11 subunit helicase for eukaryotic DNA replication. Two CMGs are assembled at origins starting from two Mcm2-7 hexamers oriented N-to-N. The orientation of CMG at a forked DNA implies that the two CMGs at an origin pass one another. (shrink)

The adaptation aftereffect plays a critical role in human development and survival. Existing studies have found that, compared with general individuals, individuals with learning disability, autism and dyslexia show a smaller amount of non-affective-based cognitive adaptation aftereffect. Nevertheless, it is unclear whether individuals with depression or depression tendency show similar phenomenon in the adaptation aftereffect, and whether such depression tendency occurs in the non-affective-based cognitive or emotional adaptation aftereffect. To address this question, the present study conducted two experiments. Experiments 1A (...) and 1B used the emotional facial expression adaptation paradigm to examine whether Chinese participants showed the emotional adaptation aftereffect and whether the emotional adaptation aftereffect was influenced by physical features of faces, respectively. Experiment 2 recruited two groups of participants, with high and low depression, respectively, to examine whether they showed differences in the emotional or cognitive adaptation aftereffect. Results showed that Chinese participants showed the typical emotional adaptation aftereffect, which was not influenced by physical features of faces. More importantly, compared to the low-depression group, the high-depression group showed a smaller emotional adaptation aftereffect, but the two groups showed a similar cognitive adaptation aftereffect. These results suggest that level of depressive symptoms is associated with the emotional adaptation aftereffect. (shrink)

By PFM, we mean a finitely generated module over a principal ideal domain; a linear sentence is a sentence that contains no disjunctive and negative symbols. In this paper, we present an algorithm which decides the truth for linear sentences on a given PFM, and we discuss its time complexity. In particular, when the principal ideal domain is the ring of integers or a univariate polynomial ring over the field of rationals, the algorithm is polynomial-time. Finally, we consider some applications (...) to Abelian groups. (shrink)

Clamp loaders are pentameric AAA+ assemblies that use ATP to open and close circular DNA sliding clamps around DNA. Clamp loaders show homology in all organisms, from bacteria to human. The eukaryotic PCNA clamp is loaded onto 3′ primed DNA by the replication factor C (RFC) hetero‐pentameric clamp loader. Eukaryotes also have three alternative RFC‐like clamp loaders (RLCs) in which the Rfc1 subunit is substituted by another protein. One of these is the yeast Rad24‐RFC (Rad17‐RFC in human) that loads a (...) 9‐1‐1 heterotrimer clamp onto a recessed 5′ end of DNA. Recent structural studies of Rad24‐RFC have discovered an unexpected 5′ DNA binding site on the outside of the clamp loader and reveal how a 5′ end can be utilized for loading the 9‐1‐1 clamp onto DNA. In light of these results, new studies reveal that RFC also contains a 5′ DNA binding site, which functions in gap repair. These studies also reveal many new features of clamp loaders. As reviewed herein, these recent studies together have transformed our view of the clamp loader mechanism. (shrink)