Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/117513
Title: FUNCTIONAL CHARACTERIZATION OF HUMAN METHYLTRANSFERASE LIKE PROTEIN 8 IN DNA DAMAGE RESPONSE
Authors: LIANG JUNXIN
Keywords: Methyltransferase, DNA damage, ATM, p53, cell cycle, STAT
Issue Date: 22-Jan-2014
Citation: LIANG JUNXIN (2014-01-22). FUNCTIONAL CHARACTERIZATION OF HUMAN METHYLTRANSFERASE LIKE PROTEIN 8 IN DNA DAMAGE RESPONSE. ScholarBank@NUS Repository.
Abstract: METHYLTRANSFERASE LIKE PROTEIN 8 (METTL8) WAS FIRST SCREENED OUT AS A STAT3 TARGET IN SEVERAL SYSTEMS IN OUR LAB. IT IS AN INTERESTING POTENTIAL NOVEL EPIGENETIC ENZYME AS IT CAN BIND S-ADENOSYL-METHIONINE AND FORM COMPLEX WITH HISTONES, ALTHOUGH THE EXACT SUBSTRATE IS STILL UNCLEAR. IT HAS SEVERAL FEATURED DOMAINS: SANT DOMAIN, SAM BINDING DOMAIN FOR METHYLTRANSFERASE ACTIVITY, NRB DOMAIN AND PS/TQ MOTIF, WHICH IS A SIGNATURE OF ATM/ATR SUBSTRATE. WE VALIDATED METTL8 AS AN ATM SUBSTRATE AND ITS BINDING WITH ATM, P53 AND HISTONES. THE ROLE OF METTL8 IN UPREGULATION OF ATM EXPRESSION AND ACTIVATION, AND ITS DOWNSTREAM PATHWAYS WAS SHOWN CONSISTENTLY IN THREE CIRCUMSTANCES: METTL8 SAM MUTANT,METTL8&METTL2 DOUBLE KD AND METTL8 KO. HOWEVER, THE OVERALL OUTPUT EFFECTS ON CELL GROWTH AND SURVIVAL DIFFER A LOT. BY USING ATM INHIBITOR KU55933, WE ALSO SHOWED CLEARLY THAT THE ATM DOWNSTREAM PATHWAY CHANGES WERE DIRECTLY AFFECTED BY ATM.
URI: http://scholarbank.nus.edu.sg/handle/10635/117513
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