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Lim, Chae-Seok,Kang, Xi,Mirabella, Vincent,Zhang, Huaye,Bu, Qian,Araki, Yoichi,Hoang, Elizabeth T.,Wang, Shiqiang,Shen, Ying,Choi, Sukwoo,Kaang, Bong-Kiun,Chang, Qiang,Pang, Zhiping P.,Huganir, Richar Cold Spring Harbor Laboratory Press 2017 Genes & development Vol.31 No.6
<P>Rapid advances in genetics are linking mutations on genes to diseases at an exponential rate, yet characterizing the gene mutation-cell behavior relationships essential for precision medicine remains a daunting task. More than 350 mutations on small GTPase BRaf are associated with various tumors, and similar to 40 mutations are associated with the neurodevelopmental disorder cardio-facio-cutaneous syndrome (CFC). Wedeveloped a fast cost-effective lentivirus-based rapid gene replacement method to interrogate the physiopathology of BRaf and similar to 50 disease-linked BRaf mutants, including all CFC-linked mutants. Analysis of simultaneous multiple patch-clamp recordings from 6068 pairs of rat neurons with validation in additional mouse and human neurons and multiple learning tests from 1486 rats identified BRaf as the key missing signaling effector in the common synaptic NMDA-R-CaMKII-SynGap-Ras-BRaf-MEK-ERK transduction cascade. Moreover, the analysis creates the original big data unveiling three general features of BRaf signaling. This study establishes the first efficient procedure that permits large-scale functional analysis of human disease-linked mutations essential for precision medicine.</P>
MutS homolog sliding clamps shield the DNA from binding proteins
Hanne, Jeungphill,Britton, Brooke M.,Park, Jonghyun,Liu, Jiaquan,Martí,n-Lí,ó,pez, Juana,Jones, Nathan,Schoffner, Matthew,Klajner, Piotr,Bundschuh, Ralf,Lee, Jong-Bong,Fishel, Richar American Society for Biochemistry and Molecular Bi 2018 The Journal of biological chemistry Vol.293 No.37
<P>Sliding clamps on DNA consist of evolutionarily conserved enzymes that coordinate DNA replication, repair, and the cellular DNA damage response. MutS homolog (MSH) proteins initiate mismatch repair (MMR) by recognizing mispaired nucleotides and in the presence of ATP form stable sliding clamps that randomly diffuse along the DNA. The MSH sliding clamps subsequently load MutL homolog (MLH/PMS) proteins that form a second extremely stable sliding clamp, which together coordinate downstream MMR components with the excision-initiation site that may be hundreds to thousands of nucleotides distant from the mismatch. Specific or nonspecific binding of other proteins to the DNA between the mismatch and the distant excision-initiation site could conceivably obstruct the free diffusion of these MMR sliding clamps, inhibiting their ability to initiate repair. Here, we employed bulk biochemical analysis, single-molecule fluorescence imaging, and mathematical modeling to determine how sliding clamps might overcome such hindrances along the DNA. Using both bacterial and human MSH proteins, we found that increasing the number of MSH sliding clamps on a DNA decreased the association of the Escherichia coli transcriptional repressor LacI to its cognate promoter LacO. Our results suggest a simple mechanism whereby thermal diffusion of MSH sliding clamps along the DNA alters the association kinetics of other DNA-binding proteins over extended distances. These observations appear generally applicable to any stable sliding clamp that forms on DNA.</P>
OGLE-2019-BLG-0362Lb: A Super-Jovian-Mass Planet around A Low-Mass Star
정선주,Jennifer C. Yee,Andrej Udalski,Andrew Gould,Michael D. Albrow,정연길,황규하,CHEONGHOHAN,Yoon-Hyun Ryu,신인구,Yossi Shvartzvald,Weicheng Zang,차상목,Dong Jin Kim,김승리,이충욱,Dong-Joo Lee,이용석,Byeong-Gon Park,Richar 한국천문학회 2022 Journal of The Korean Astronomical Society Vol.55 No.4
We present the analysis of a planetary microlensing event OGLE-2019-BLG-0362 with a short-duration anomaly (~0.4 days) near the peak of the light curve, which is caused by the resonant caustic. The event has a severe degeneracy with $\delcs = 0.9$ between the close and the wide binary lens models both with planet-host mass ratio $q \simeq 0.007$. We measure the angular Einstein radius but not the microlens parallax, and thus we perform a Bayesian analysis to estimate the physical parameters of the lens. We find that the OGLE-2019-BLG-0362L system is a super-Jovian-mass planet $M_{\rm p}=3.26^{+0.83}_{-0.58}~M_{\rm J}$ orbiting an M dwarf $M_{\rm h}=0.42^{+0.34}_{-0.23}~M_{\odot}$ at a distance $D_{\rm L} =5.83^{+1.04}_{-1.55}$ kpc. The projected star-planet separation is $a_{\perp} = 2.18^{+0.58}_{-0.72}~{\rm AU}$, which indicates that the planet lies beyond the snow line of the host star.