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Seongseop Kim,심재갈 한국분자세포생물학회 2008 Molecules and cells Vol.25 No.1
Pyrimidine antagonists including 5-Fluorouracil (5- FU) have been used in chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a mainstay treatment for colorectal cancer. It is a pro-drug that is converted to the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5-FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One of the major obstacles to successful chemotherapy is the resistance of cancer cells to anti-cancer drugs. Therefore, it is important to elucidate resistance mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a model system to investigate the mechanism of resistance to 5- FU, which induces germ cell death and inhibits larval development in C. elegans. We screened 5-FU resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants out of 72,000 F1 individuals screened, and mapped them into three complementation groups. We propose that C. elegans could be a useful model system for studying mechanisms of resistance to anti-cancer drugs.
Ecological impacts of calving of the Nansen Ice Shelf in Antarctica
Seongseop Park,Jean-Baptiste Thiebot,Jeong-Hoon Kim,Hosung Chung,Won Young Lee 대한지질학회 2021 대한지질학회 학술대회 Vol.2021 No.10
By calving of the Nansen Ice Shelf in 2016, a newly accessible marine area has opened. For estimating the ecological impacts after calving, It is important to observe this region. In this study, we examined the foraging behavior of Adélie penguins in December 2018, by tracking 27 penguins during their at-sea trips using GPS, depth and video loggers. The penguins mainly foraged within 88.2 ± 42.9 km of their colony, for 23.4 ± 6.8 h. Five penguins headed south to the newly exposed habitat along the Nansen Ice Shelf, whereas 22 penguins exploited previously available foraging areas. In the calved region, the penguins were diving into shallow areas more often than did the other penguins. These results show that Adélie penguins on Inexpressible Island had explored the newly exposed area after calving. We conclude that the penguins respond to newly available habitat following stochastic environmental events, either through information sharing at the colony, and/or by balancing prey availability per capita across the foraging sites. The results of this study may provide insights for evaluating the ecological importance of this area for conservation.
Kim, Seongseop,Park, Dae-Hun,Shim, Jaegal Korean Society for Molecular Biology 2008 Molecules and cells Vol.26 No.4
<P>5-Fluorouracil (5-FU), a pyrimidine antagonist, has a long history in cancer treatment. The targeted pyrimidine biosynthesis pathway includes dihydropyrimidine dehydrogenase (DPD), which converts 5-FU to an inactive metabolite, and thymidylate synthase (TS), which is a major target of 5-FU. Using Caenorhabditis elegans as a model system to study the functional and resistance mechanisms of anti-cancer drugs, we examined these two genes in order to determine the extent of molecular conservation between C. elegans and humans. Overexpression of the worm DPD and TS homologs (DPYD-1 and Y110A7A.4, respectively) suppressed germ cell death following 5-FU exposure. In addition, DPYD-1 depletion by RNAi resulted in 5-FU sensitivity, while treatment with Y110A7A.4 RNAi and 5-FU resulted in similar patterns of embryonic death. Thus, the pathway of 5-FU function appears to be highly conserved between C. elegans and humans at the molecular level.</P>
Kim, Seongseop,Park, Dae‐,Hun,Kim, Tai Hoon,Hwang, Moogak,Shim, Jaegal Blackwell Publishing Ltd 2009 The FEBS journal Vol.276 No.17
<P>Pyrimidine biosynthesis enzymes function in many cellular processes and are closely associated with pyrimidine antagonists used in cancer chemotherapy. These enzymes are well characterized from bacteria to mammals, but not in a simple metazoan. To study the pyrimidine biosynthesis pathway in <I>Caenorhabditis elegans</I>, we screened for mutants exhibiting resistance to the anticancer drug 5‐fluorouracil (5‐FU). In several strains, mutations were identified in ZK783.2, the worm homolog of human uridine phosphorylase (UP). UP is a member of the pyrimidine biosynthesis family of enzymes and is a key regulator of uridine homeostasis. <I>C.?elegans</I> UP homologous protein (UPP‐1) exhibited both uridine and thymidine phosphorylase activity <I>in vitro</I>. Knockdown of other pyrimidine biosynthesis enzyme homologs, such as uridine monophosphate kinase and uridine monophosphate synthetase, also resulted in 5‐FU resistance. Uridine monophosphate kinase and uridine monophosphate synthetase proteins are redundant, and show different, tissue‐specific expression patterns in <I>C.?elegans.</I> Whereas pyrimidine biosynthesis pathways are highly conserved between worms and humans, no human thymidine phosphorylase homolog has been identified in <I>C.?elegans.</I> UPP‐1 functions as a key regulator of the pyrimidine salvage pathway in <I>C.?elegans</I>, as mutation of <I>upp‐1</I> results in strong 5‐FU resistance.</P>