서울대학교 생물정보연구소와 생물정보학 협동과정 공동 주최로 특별 세미나를 아래와 같이 열고자 하오니, 많은 참여 바랍니다.

일시: 2016년 5월 11일 수요일 오전 11시

연사: 명경재 (IBS유전체항상성연구단)

장소: 서울대학교 25동 411호

[Title] Identification of a novel chemotherapeutic agent specific for tumors with DNA mismatch

repair deficiencies

[Abstract] Impairing the proliferation of rapidly dividing cancer cells is the primary mechanism for most conventional chemotherapeutic agents. However, cancer cells with DNA mismatch repair (MMR) deficiencies, such as Lynch Syndrome tumors, are resistant to most conventional chemotherapeutic agents since these cancer cells can continue to divide even with extensive DNA lesions. Here we have identified compound F as a small molecule that selectively kills MutSα-deficient cancer cells. Compound F binds preferentially to mismatched DNA and induces a DNA damage response in a mismatch repair-dependent manner. In MutSα-proficient cells, compound F binds to MutSα and induces dissociation of CHK2 from MutSα leading to S phase arrest and cell survival. In contrast, compound F-mismatched DNA adducts do not induce a DNA damage response in MutSα-deficient cells. Continued replication in the presence of compound F results in a high number of DNA double-strand breaks and ultimately leads to apoptosis of the MutSα-deficient cells. Consistently, compound F treatment specifically shrinks MutSα-deficient xenograft tumors. We believe that compound F offers the potential of an improved treatment option for patients with tumors with a DNA MMR deficiency.

[Education]

[Professional Experiences]

[Recent Publications]

1. Kimberly J. Zanotti, Robert W. Maul, William Yang, Yongjun Choi, Jennifer Fox, KyungjaeMyung, Huseyin Saribasak, and Patricia J. Gearhart. (2014) ATAD5 deficiency decreases B-cell division and Igh recombination. J. Immunology 194:35-42 PMID: 25404367

2. Jun Che, Stephanie Smith, Yoo Jung Kim, Eun Yong Shim, KyungjaeMyung, and Sang Eun Lee. Hyper-acetylation of Histone H3 K56 limits break-induced replication by inhibiting extensive repair synthesis. (2015) PLoS Genet. 11:e1004990 PMID: 25705897

3. Claudia M. Nicolae, Erin R. Aho, Katherine N. Choe, Deokjae Lee, KyungjaeMyung, and George-Lucian Moldovan. (2015) A novel role for the mono-ADP-ribosyltransferase PARP14/ATRD8 in promoting homologous recombination and protecting against replication stress. Nucleic Acid Res. 43:3143-3153 PMID:25753673

4. Wen-Pin Su, Sen-Huei Hsu, Li-Chiao Chia, Jui-yang Lin, Song-Bin Chang, Zong-da Jiang, Yi-Ju Lin, Min-Yu Shih, Yi-Cheng Chen, Mau-Sun Chang, Wen-Bin Yang, Jan-Jong Huan, Po-cheng Hung, Wei-Sheng Wu, KyungjaeMyung, and Hungjiun Liaw. (2015) Combined interactions of PHD and chromodomain regulate NuA4 activity at DNA double-strand breaks. Genetics 115:184432 [Epub ahead of print] PMID: 26564157

5. Nam Soo Lee, Hee Jin Chung, Hyoung-June Kim, Seo Yun Lee, Jae-Hoon Ji, Yoojeong Seo, Seung Hun Han, Minji Choi, Miyong Yun, Seok-Geun Lee, KyungjaeMyung,Yonghwan Kim, Ho Chul Kang, and Hongtae Kim. Yeast two-hybrid screen identifies TRAIP/RNF206 required for recruitment of RAP80 to sites of DNA damage. Nature Communication In press

6. Malleswara Rao Kuram, Woo Gyum Kim, KyungjaeMyung, and Sung You Hong. Copper-catalyzed direct synthesis of 1,2,4-oxadiazoles from amides and organic nitriles via oxidative N-O bond formation. European J. Organic Chem. In press

7. Sunsil Choi, Eun-Sun Kim, Ji-Eun Jung, David P. Marciano, Ala Jo, Ja Young Koo, Soo Youn Choi, Yong Ryoul Yang, Hyun-Jun Jang, Eung-Kyun Kim, Jiyoung Park, Hyug Moo Kwon, In Hee Lee, Seung Bum Park, KyungjaeMyung, Pann-Ghill Suh, Patrick R. Griffin, Jang Hyun Choi. PPARg antagonist Gleevec improves insulin sensitivity and promotes the browning of white adipose tissue. Diabetes In press

8. Deokjae Lee, Hungjiun Liaw, Roger Woodgate, and KyungjaeMyung. SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR-dependent manner. In preparation

9. Yongliang Zhang, Jennifer T. Fox, Gene Elliot, Ganesha Rai, Srilatha Sakamuru, Ruili Huang, Menghang Xia, Hee Dong Park, David Maloney, and KyungjaeMyung. Identification of a novel chemotherapeutic agent specific for tumors with DNA mismatch repair deficiencies. In preparation

10. Bijoy Mathew, Him Chan Jeon, Jeong Hyeon Lee, Jin Chul Kim, Hyun Ji Yang, Tae Joo Shin, KyungjaeMyung, Sang Kyu Kwak, Ja-Hun Kwak, Sung You Hong. C-H Bond Arylation of Anilides inside Copper-Exchanged Zeolites. In preparation

서울대학교 생물정보연구소

생물정보학 협동과정 공동주최