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ÁöÀçÈÆ ±³¼ö´Â “1980³â´ë ÃÊ, ¼¼Æ÷ ³» ´Ü¹éÁúÀÇ ºÐÇØ°¡ À¯ºñÄûƾ(ubiquitin)¿¡ ÀÇÇØ ÁßÀçµÈ´Ù´Â °³³äÀÌ ¼º¸³µÈ ÀÌ·¡ ¼ö¸¹Àº ¿¬±¸ÀÚµéÀÌ ÀÌ¿¡ ´ëÇÑ ¿¬±¸¿¡ ¸ÅÁøÇØ¿Ô½À´Ï´Ù. ±×·¯³ª Àΰ£ÀÇ À¯Àüü ¾È¿¡ Á¸ÀçÇÒ °ÍÀ¸·Î ÃßÁ¤µÇ´Â ¾à 500°³ ÀÌ»óÀÇ À¯ºñÄûƾȭ È¿¼Ò(E3 ubiquitin ligases) Áß ±ØÈ÷ ÀϺθ¸ÀÌ À¯Àüü ¼Õ»ó ¹× º¹±¸¿¡ °ü¿©ÇÑ´Ù°í ±Ô¸íµÇ¾úÀ» »Ó ³ª¸ÓÁö´Â ¿©ÀüÈ÷ ¹ÌÁöÀÇ ¿µ¿ª¿¡ ¸Ó¹°·¯ ÀÖ´Â °ÍÀÌ »ç½ÇÀÔ´Ï´Ù”¶ó°í ¹àÇû´Ù. ÀÌ´Â °¢°¢ÀÇ À¯ºñÄûƾȭ È¿¼Ò°¡ Àú¸¶´Ù ´Ù¸¥ ±âÁú ´Ü¹éÁú°ú »óÈ£ÀÛ¿ëÇϱ⠶§¹®À¸·Î, ±× ¿ªÇÒÀ» ¹àÇô³»±â À§Çؼ± ¼ö½Ê¸¸ °³¿¡ ´ÞÇÏ´Â ´Ü¹éÁúÀ» °¢°¢ÀÇ È¿¼Ò¿Í ÀÏÀÏÀÌ ´ëÁ¶ÇÏ°í ¹ÝÀÀÀ» ÁöÄѺÁ¾ßÇÏ´Â ¾î·Á¿òÀÌ ÀÖ¾ú´Ù. ÀÌ¿¡ Áö ±³¼ö°¡ Á¦½ÃÇÑ ¹æ¹ýÀº DNA ¼Õ»ó ¹× º¹±¸ ½ÅÈ£¿¡ °ü¿©ÇÏ´Â ´Ü¹éÁúÀ» ƯÁ¤È­ÇÏ°í, ÀÌ¿¡ ´ëÀÀÇÏ´Â À¯ºñÄûƾȭ È¿¼Ò¸¦ °Ë»öÇس»´Â ¹æ½ÄÀ¸·Î ±âÁ¸ÀÇ ±âÁú ´Ü¹éÁú ƯÀÌÀû À¯ºñÄûƾȭ È¿¼Ò°¡ ¾Æ´Ñ (±âÁú ´Ü¹éÁúÀ» Ç¥ÀûÀ¸·Î ÇÏÁö ¾Ê´Â) ºñ±âÁú À¯ºñÄûƾ üÀÎ (free ubiquitin chains)ÀÌ À¯Àüü ¼Õ»ó½ÅÈ£ ¹× º¹±¸¿¡ ÇʼöÀûÀÓÀ» ¹àÈûÀ¸·Î½á ±âÁ¸ ¿¬±¸ÀÇ Æз¯´ÙÀÓÀ» Çõ½ÅÀûÀ¸·Î º¯È­½Ãų °ÍÀ̶õ ÆòÀ» ¹Þ°í ÀÖ´Ù.

“¹Ì·¡°úÇÐÀÇ ÁöÇâÁ¡Àº ‘Àΰ£º¹ÁöÀÇ Ã¢Ãâ’ÀÔ´Ï´Ù”
¶ÇÇÑ, ÁöÀçÈÆ ±³¼ö´Â À¯Àüü ¼Õ»ó¿¡ ÀÇÇØ ¹ß»ýÇÏ´Â À¯ÀüÀû Áúº´ÀÎ ‘Àª¸®¾ö½º ÁõÈıº(Williams Syndrome)’ÀÇ ÇÙ½É Á¶ÀýÀÎÀÚ ‘WSTF’¿¡ ´ëÇØ ¿¬±¸ÇØ¿Ô´Ù. ƯÈ÷, ±âÁ¸ DNA ¼Õ»ó ¹× º¹±¸¿¡ °üÇÑ ¿¬±¸°¡ ATM/ATR ÀλêÈ­È¿¼ÒÀÇ Ç¥Àû ´Ü¹éÁú ¿¬±¸¿¡ ÃÊÁ¡ÀÌ ¸ÂÃçÁ³´ø °Í°ú´Â ´Þ¸® ±×´Â DNA ¼Õ»ó ¹× º¹±¸°úÁ¤¿¡¼­ WSTF°¡ ¾î¶² ¿ªÇÒÀ» ÇÏ´ÂÁö¸¦ ±Ô¸íÇÏ°íÀÚ ³ë·ÂÇØ¿ÔÀ¸¸ç, ³ª¾Æ°¡ WSTF¿¡ ÀÇÇØ Á¶ÀýµÇ´Â °áÇմܹéÁú ºÐ¼®À» ÅëÇØ Å©·Î¸¶Æ¾ º¹ÇÕü¿Í È÷½ºÅæ ¼ö½ÄÈ­ ´Ü¹éÁú °£ÀÇ »óÈ£ÀÛ¿ëÀ» ÀÌÇØÇÏ´Â µ¥ ÁÖ·ÂÇß´Ù. ±× °úÁ¤¿¡¼­ Áö ±³¼ö ¿¬±¸ÆÀÀº ±¹³» ÃÖÃÊ·Î ‘DNA ¼Õ»óºÎÀ§ ƯÀÌÀû Àü»çÁ¶Àý ½Ã½ºÅÛ’À» ±¸ÃàÇÏ¿© DNA ¼Õ»ó ¹× º¹±¸ ½ÅÈ£¿¡ ÀÖ¾î Àü»çÁ¶ÀýÀÎÀÚ¿Í Å©·Î¸¶Æ¾ º¹ÇÕü°¡ ¼öÇàÇÏ´Â ¿ªÇÒÀ» ±Ô¸íÇÏ´Â µ¥ ¼º°øÇßÀ¸¸ç, ‘Inducible mCherry-LacI-FokI system’À» ÇÔ²² »ç¿ëÇØ DNA ¼Õ»ó ¹× º¹±¸ ½ÅÈ£¿¡ °ü¿©ÇÏ´Â »õ·Î¿î ´Ü¹éÁúÀ» º¸´Ù ½Å¼ÓÇÏ°í Á¤È®ÇÏ°Ô Ã£¾Æ³¾ ¼ö ÀÖ´Â ±â¼úÀ» ±¸ÇöÇϱ⿡ À̸£·¶´Ù. À¯Àüü Çâ»ó¼º ¿¬±¸ ºÐ¾ß¿¡¼­ Áö ±³¼öÀÇ ¼º°ú°¡ ÁÖ¸ñ¹Þ´Â °ÍÀº ¹Ù·Î ÀÌ·¯ÇÑ ±î´ßÀÌ´Ù. ±×°¡ °³¹ßÇÑ ½Ã½ºÅÛÀ» ÀÌ¿ëÇϸé À¯Àüü ¼Õ»ó ¹× º¹±¸ ½ÅÈ£¿¡¼­ »õ·Î¿î ´Ü¹éÁúÀ» ºü¸£°Ô °Ë»öÇÏ´Â °ÍÀÌ °¡´ÉÇØÁö±â ¶§¹®ÀÌ´Ù. ±×´Â ÀÌ ½Ã½ºÅÛÀ» È°¿ëÇÑ ÈÄ¼Ó ¿¬±¸¸¦ ÅëÇØ À¯ºñÄûƾȭ È¿¼ÒÀÇ ±â´É ±Ô¸í°ú WSTF¿¡ ´ëÇÑ »õ·Î¿î ¹æÇ⼺À» Á¦½ÃÇÒ ¼ö ÀÖÀ» °ÍÀ¸·Î Àü¸ÁÇÏ°í ÀÖÀ¸¸ç, ³ª¾Æ°¡ ºñÁ¤»óÀû ±¸Á¶¸¦ °¡Áö´Â ´Ü¹éÁú, ¼Õ»óµÈ ´Ü¹éÁú¿¡ ÀÇÇÑ À¯ÀüÀû Áúº´À» Ä¡·á, ¿¹¹æÇÏ´Â µ¥¿¡ ȹ±âÀûÀÎ ÀüȯÁ¡ÀÌ µÉ ¼ö ÀÖÀ¸¸®¶ó ±â´ëÇÏ°í ÀÖ´Ù. 
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Creative approaches bring solutions to future of humanity
Prof. Ji Jae-hoon of Ajou University School of Medicine Genomic Instability Research Center 

A new paradigm for ubiquitin ligases researches

We all die one day and so does proteins. Tens of millions of proteins in our body have different life span. To find out what causes the death of protein can be a key to find out what causes aging and to find preventions and cures of diseases. 

Prof. Ji Jae-hoon of Ajou University School of Medicine Genomic Instability Research Center has carried on research on the causes of genetic diseases and their mechanisms for many years. Based on the result of the research, he recently has launched a new research on finding the functions of ‘ubiquitin ligases’ that plays an important part in proteolysis and signal transduction.

“The conception ‘proteolysis is mediated by ubiquitin’ was established in early 80s and a lot of researchers have poured their passion and energy in the field ever since. However, only a few among assumed 500 E3 ubiquitin ligases have been proven to involve in DNA damages and recoveries and the rests are still remained obscure” explains Ji. 

This is because each ubiquitin ligase has each different trait of protein and that they interact. It means that researchers have to compare hundreds of thousands of proteins with each enzyme and check on the reactions. 

To simplify the procedure, Prof. Ji specified the proteins that involve in DNA damage and recovery signals from which he searched the responding ubiquitin ligases. This way, he revealed the fact that the ‘free ubiquitin chains’, but not the ‘specific ubiquitin ligases (not targeted organic protein)’, is a must for DNA damage and recovery signals. Ji’s finding is received by people that it will innovatively change the paradigm of the existing research directions. 

“Human welfare is the direction of future science”

Prof. Ji also has been carrying on research on ‘WSTF’, the core modulator of ‘Williams Syndrome’, a genetic disease caused by DNA damages. Unlike the existing DNA damage and recovery researches that focused on the targeted protein of ATM/ART phosphorylating enzyme, Ji exerted instead his effort in finding what role WSTF does during the DNA damage and recovery process. Further more, he focused on analyzing the binding protein controlled by WSTF to understand the interactions between chromatin complex and histone modified protein. 

During these processes, the research team of Ji has built ‘DNA Damaged Parts Specific Transcriptional Control System’ for the first time in Korea. As a result, the team succeeded in revealing the roles of transcriptional control factors and chromatin complex in regard to DNA damages and recoveries. 

Also, the team used ‘Inducible mCherry-LacI-FokI system’ to realize the technologies that can find more precisely the new proteins related to DNA damage and recovery signals in speed. This is the reason that Ji’s research achievements are coming into attention in the field of DNA improvement research because his developments of the system enabled us to search faster the new proteins in relation with DAN damage and recovery signals. 

Ji predicts that follow up researches of the system can suggest a new direction for revealing the functions of ubiquitin ligases and WSTF, and for finding cures of the DNA diseases caused by abnormal or damaged proteins. Ji expects that it can also play an epoch-making turning point for prevention of diseases. 

He adds that it is important for the government to provide research-friendly environments and a good foundation for manpower fostering. Also, the research results and achievements must be shared with those who have made contributions including students. This way, Korea can grow as a global science and technology powerhouse. 

The demand for convergence science is increasing more than ever today. And the competition to get the best seats of the benefit is fierce among advanced countries. In this respect, it is worthwhile to take note what Ji says “Human welfare is the direction of future science”.


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