Late Effects Studies (Laboratory of DNA Damage Signaling)

kao
Minoru Takata, M.D., Ph.D. Professor  btn

Human genome is under constant attack from (1) exogenous DNA damage such as double stranded breaks due to ionizing irradiation, and (2) endogenous DNA damage originated from cellular metabolism and replication stress. To handle such damages appropriately is of foremost importance as self-defense mechanisms in all cells of our body. In patients with genome instability disorders, the mechanisms that prevent, sense, tolerate, and repair genome damages are defective. We are focusing on the molecular mechanisms of protecting the genome from both basic and clinical viewpoints.

Research and Education

Our research goal is to elucidate the mechanisms of signal transduction pathways initiated by genome damage and stress. In particular, we are focusing on replication stress by carcinogenic events or by DNA damage created by endogenous metabolites. We are interested in human pathological condition called Fanconi anemia (FA), which is a rare hereditary disorder. FA is characterized by birth defects, progressive aplastic anemia (failure of hematopoietic stem cells), and development of leukemia and solid tumors. FA is caused by a defect in the FA pathway, in which 18 FA genes together function to orchestrate activities of DNA repair at the site of DNA damage or replication stress. We are working on identification of novel FA genes by analysis of Japanese FA patients, or mechanisms to stabilize non-coding DNA regions such as common fragile sites.
The projects for graduate students would relate to two important aspects to achieve our goal: (1) screening aiming to discover novel molecules, and (2) genetic analysis of their function. Our lab tries to provide environment to support each individual’s project by sharing materials and methodologies in intimate interactions.

 

SliderInteraction between the key FA molecule FANCD2 and CtIP that resects DNA ends during homologous recombination as detected by the Proximal Ligation Assay

r-079-2Laboratory group photo (2011)


Recent Publications

1.Mutations in the Gene Encoding the E2 Conjugating Enzyme UBE2T Cause Fanconi Anemia. Hira A, Yoshida K, Sato K, Okuno Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Shimamoto A, Tahara H, Ito E, Kojima S, Kurumizaka H, Ogawa S, Takata M, Yabe H, Yabe M. Am J Hum Genet. 2015 Jun 4;96(6):1001-7. doi: 10.1016/j.ajhg.2015.04.022.PMID: 26046368
2.Ishii, K., Ishiai, M., Morimoto, H., Kanatsu-Shinohara, M., Niwa, O., Takata, M. and Shinohara, T. The Trp53-Trp53lip1-Tnfrs10b pathway regulates radiation response of mouse spermatogonial stem cells. Stem Cell Reports, 3(4), 676-689, 2014.
3.FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair. Unno J, Itaya A, Taoka M, Sato K, Tomida J, Sakai W, Sugasawa K, Ishiai M, Ikura T, Isobe T, Kurumizaka H, Takata M. Cell Rep. 2014 May 22;7(4):1039-47. doi: 10.1016/j.celrep.2014.04.005. Epub 2014 May 1.
4.Variant ALDH2 is associated with accelerated progression of bone marrow failure in Japanese Fanconi anemia patients. Hira A, Yabe H, Yoshida K, Okuno Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Nakamura J, Kojima S, Ogawa S, Matsuo K, Takata M, Yabe M. Blood. 2013 Oct 31;122(18):3206-9. doi: 10.1182/blood-2013-06-507962.
5.A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair. Tomida J, Itaya A, Shigechi T, Unno J, Uchida E, Ikura M, Masuda Y, Matsuda S, Adachi J, Kobayashi M, Meetei AR, Maehara Y, Yamamoto K, Kamiya K, Matsuura A, Matsuda T, Ikura T, Ishiai M, Takata M. Nucleic Acids Res. 2013 Aug;41(14):6930-41.

Laboratory

Professor Minoru Takata
Associate professor Masamichi Ishiai
Tel: +81-075-753-7563
FAX:+81-075-753-7564
E-mail: mtakata@house.rbc.kyoto-u.ac.jp
URL:http://house.rbc.kyoto-u.ac.jp/Late_Effect/Japanese_site/Welcome.html