Claspin plays multiple important roles in regulation of DNA replication as a mediator for the cellular response to replication stress, an integral replication fork factor that facilitates replication fork progression and a factor that promotes initiation by recruiting Cdc7 kinase. Here, we report a novel role of Claspin in growth recovery from serum starvation, which requires the activation of PI3 kinase (PI3K)-PDK1-Akt-mTOR pathways. In the absence of Claspin, cells do not proceed into S phase and eventually die partially in a ROS- and p53-dependent manner.
View Article and Find Full Text PDFReplication stress has been suggested to be an ultimate trigger of carcinogenesis. Oncogenic signal, such as overexpression of CyclinE, has been shown to induce replication stress. Here, we show that various biological stresses, including heat, oxidative stress, osmotic stress, LPS, hypoxia, and arsenate induce activation of Chk1, a key effector kinase for replication checkpoint.
View Article and Find Full Text PDFEntrepreneurial intention is an important condition for promoting substantive entrepreneurial behavior, which in turn alleviates employment pressure and promotes sustainable economic and social development. Based on national survey data of university students, descriptive statistical analysis of variables and binary logistic regression analysis were used to empirically analyze the factors influencing university students' entrepreneurial intentions in five aspects, including innate endowment, acquired characteristics, entrepreneurship courses, and entrepreneurial practice, and social support. The regression results showed that both the factors of innate endowment and acquired characteristics passed the significance test.
View Article and Find Full Text PDFA multitude of studies have suggested potential factors that influence internet security awareness (ISA). Some, for example, used GDP and nationality to explain different ISA levels in other countries but yielded inconsistent results. This study proposed an extended knowledge-attitude-behaviour (KAB) model, which postulates an influence of the education level of society at large is a moderator to the relationship between and .
View Article and Find Full Text PDFBackground: The optimal antibiotic regimen for the medical management of acute appendicitis remains unknown due to a lack of head-to-head comparisons between different antibiotic regimens.
Methods: We systematically searched the PubMed, EMBASE, Scopus and Cochrane Central Register of Controlled Trials databases from their inception through to August 2020. We selected randomized controlled trials (RCTs) or observational studies comparing antibiotic therapy and appendectomy as the initial treatment for adult or paediatric patients with acute appendicitis.
Replication checkpoint is essential for maintaining genome integrity in response to various replication stresses as well as during the normal growth. The evolutionally conserved ATR-Claspin-Chk1 pathway is induced during replication checkpoint activation. Cdc7 kinase, required for initiation of DNA replication at replication origins, has been implicated in checkpoint activation but how it is involved in this pathway has not been known.
View Article and Find Full Text PDFMrc1 and its vertebrate homologue Claspin serve as a mediator for replication stress checkpoint signaling, receiving the signal from Mec1/Rad3/ATR sensor kinase and transmitting it to the effector Rad53/Cds1/Chk1 kinase. They are likely to be a part of the replisome and facilitate the S-phase progression by promoting replication fork progression. Recent reports on Mrc1/Claspin indicate their new role in regulating the replication initiation through interaction with Cdc7, a key conserved serine-threonine kinase that triggers firing at each replication origin.
View Article and Find Full Text PDFClaspin transmits replication stress signal from ATR to Chk1 effector kinase as a mediator. It also plays a role in efficient replication fork progression during normal growth. Here we have generated conditional knockout of Claspin and show that Claspin knockout mice are dead by E12.
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