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Keiichi Takata, PhD

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Smithville, TX

Research Interests

A DNA interstrand crosslink (ICL) isextremely toxic to cells because it prevents the separation of the two strandsof a DNA duplex, which is essential for cell survival. Because of their hightoxicity especially to rapidly growing cancer cells, several ICL-inducing agentsare used for cancer chemotherapy. Natural compounds such as formaldehyde andpsoralen are also capable of inducing ICLs and thus perturb genome integrity. Understandingthe molecular mechanisms of ICL processing will reveal (1) how cancer cellsgain ICL-resistance and (2) how we maintaingenomeintegrity against ICL-inducingnatural compounds. In Drosophila,mutations in the mus308 locus causehypersensitivity to ICL-inducing agents. Characterization of its humanhomologs, DNA helicase HELQ and DNA polymerase POLN will provide a new avenueof research into ICL repair. Our research has focused on exploring thebiological and biochemical mechanisms of HELQ and POLN. HELQ participates in ICLtolerance with ATR and the RAD51 paralogs. Human POLN has the ability toperform translesion DNA synthesis past ICL lesions. However, POLN favorsincorporation of T opposite template G, resulting in GC to AT transition, whichis the most frequently identified point mutation in cancer cells. POLN has thepotential to introduce point mutations. Our research will provide insights intohow ICLs are processed in human cells and will improve the use of ICL compoundsin cancer therapy.

Office Address

The University of Texas MD Anderson Cancer Center
1808 Park Road 1C
PO Box 389
Unit Number: 116
Smithville, TX 78957
Room Number: SRD1.103
Phone: 512-237-6523
Fax: 512-237-6532

Education & Training

Degree-Granting Education

2004 Tokyo University of Science, Tokyo, Japan, PHD, Biological Science

Postgraduate Training

2008-2009 Postdoctoral Researcher, The University of Texas MD Anderson Cancer Center, Smithville, TX, Richard D. Wood
2004-2009 Postdoctoral Researcher, University of Pittsburgh, Hillman Cancer Center, Pittsburgh, PA, Richard D. Wood

Selected Publications

Peer-Reviewed Original Research Articles

1. Takata K, Reh S, Tomida J, Person MD, Wood RD. Human DNA helicase HELQ participates in DNA interstrand crosslink tolerancewith ATR and RAD51 paralogs. Nat Commun 4:2338, 2013. PMCID: PMC3778836.
2. Christov PP, Yamanaka K, Choi JY, Takata K, Wood RD, Guengerich FP, Lloyd RS, Rizzo CJ. Replication of the 2,6-Diamino-4-hydroxy-N(5)-(methyl)-formamidopyrimidine (MeFapy-dGuo) Adduct by Eukaryotic DNA Polymerases. Chem Res Toxicol 25(8):1652-61, 8/20/2012. e-Pub 7/6/2012. PMCID: PMC3682502.
3. Takata K, Arana ME, Seki M, Kunkel TA, Wood RD. Evolutionary conservation of residues in vertebrate DNA polymerase N conferring low fidelity and bypass activity. Nucleic Acids Res 38(10):3233-3244, 6/2010. e-Pub 2/9/2010. PMCID: PMC2879524.
4. Yamanaka K, Minko IG, Takata K, Kolbanovskiy A, Kozekov ID, Wood RD, Rizzo CJ, Lloyd RS. Novel enzymatic function of DNA polymerase nu in translesion DNA synthesis past major groove DNA-peptide and DNA-DNA cross-links. Chem Res Toxicol 23(3):689-695, 3/15/2010. PMCID: PMC2838406.
5. Arana ME, Takata K, Garcia-Diaz M, Wood RD, Kunkel TA. A unique error signature for human DNA polymerase nu. DNA Repair (Amst) 6(2):213-23, 2/2009. PMCID: PMC1950682.
6. Nakamura R, Takeuchi R, Takata K, Shimanouchi K, Abe Y, Kanai Y, Ruike T, Ihara A, Sakaguchi K. TRF4 is involved in polyadenylation of snRNAs in Drosophila melanogaster. Mol Cell Biol 28(21):6620-6631, 11/2008. e-Pub 9/2/2008. PMCID: PMC2573236.
7. Saitoh T, Kuramochi K, Imai T, Takata K, Takehara M, Kobayashi S, Sakaguchi K and Sugawara F. Pdodphyllotoxin directly binds a hinge domain in E2 of HPV and inhibits and E2/E7 interaction in vitro. Bioorg Med Chem 16(10):5815-5825, 5/2008.
8. Kanai Y, Ishikawa G, Takeuchi R, Ruike T, Nakamura R, Ihara A, Ohashi T, Takata K, Kimura S and Sakaguchi K. DmGEN shows a flap endonuclease activity, cleaving the blocked-flap structure and model replication fork. FEBS J 274(15):3914-3927, 8/2007.
9. Ruike T, Takeuchi R, Takata K, Oshige M, Kasai N, Shimanouchi K, Kanai Y, Nakamura R, Sugawara F and Sakaguchi K. Characterization of a second proliferating cell nuclear antigen (PCNA2) from Drosophila melanogaster. FEBS J 273(22):5062-5073, 11/2006.
10. Murakami S, Kamisuke S, Takata K, Kasai N, Kimura S, Mizushina Y, Ohta K, Sugawara F and Sakaguchi K. Site directed mutational analysis of structural interactions of low molecule compounds binding to the N-terminal 8 kDa domain of DNA polymerase beta. Biochem Biophys Res Commun 350(1):7-16, 11/2006.
11. Morimura T, Noda N, Kato Y, Watanabe T, Saitoh T, Yamazaki T, Takata K, Aoki S, Ohta K, Ohshige M, Sakaguchi K and Sugawara F. Identification of antibiotic clarithromycin binding peptide displayed by T7 phage particles. J Antibiot (Tokyo) 59(10):625-632, 10/2006.
12. Takata K, Shimizu T, Iwai S, Wood RD. Human DNA polymerase N (POLN) is a low fidelity enzyme capable of error-free bypass of 5S-thymine glycol. J Biol Chem 281(33):23445-55, 8/18/2006. e-Pub 6/19/2006. PMID: 16787914.
13. Shimanouchi K, Takata K, Yamaguchi M, Murakami S, Ishikawa G, Takeuchi R, Kanai Y, Ruike T, Nakamura R, Abe Y, Sakaguchi K. Drosophila damaged DNA binding protein 1 contributes to genome stability in somatic cells. J Biochem 139(1):51-58, 1/2006. PMID: 16428319.
14. Ishikawa G, Kanai Y, Takata K, Takeuchi R, Shimanouchi K, Ruike T, Furukawa T, Kimura S and Sakaguchi K. DmGEN, a novel RAD2 family endo-exonuclease from Drosophila melanogaster. Nucleic Acids Res 32(21):6251-6259, 12/2004.
15. Takata K, Shimanouchi K, Yamaguchi M, Murakami S, Ishikawa G, Takeuchi R, Kanai Y, Ruike T, Nakamura R, Abe Y and Sakaguchi K. Damaged DNA binding protein 1 in Drosophila defense reactions. Biochem Biophys Res Commun 323(3):1024-1031, 10/2004.
16. Takata K, Yoshida H, Yamaguchi M and Sakaguchi K. Drosophila damaged DNA-binding protein 1 is an essential factor for development. Genetics 168(2):855-865, 10/2004.
17. Takeuchi R, Oshige M, Uchida M, Ishikawa G, Takata K, Shimanouchi K, Kanai Y, Ruike T, Morioka H and Sakaguchi K. Purification of Drosophila DNA polymerase zeta by REV1 protein-affinity chromatography. Biochem J 382(Pt 2):535-543, 9/2004.
18. Ishibashi T, Kimura S, Yamamoto T, Furukawa T, Takata K, Uchiyama Y, Hashimoto J and Sakaguchi K. Rice UV-damaged DNA binding protein homologues are most abundant in proliferating tissues. Gene 308:79-87, 4/2003.
19. Takata K, Inoue YH, Hirose F, Murakami S, Shimanouchi K, Sakimoto I, Sakaguchi K. Spatio-temporal expression of Drosophila mitochondrial transcription factor A during development. Cell Biol Int 27(4):361-374, 2003. PMID: 12788053.
20. Takata K, Ishikawa G, Hirose F, Sakaguchi K. Drosophila damage-specific DNA-binding protein 1 (D-DDB1) is controlled by the DRE/DREF system. Nucleic Acids Res 30(17):3795-3808, 9/1/2002. PMCID: PMC137413.
21. Takata K, Yoshida H, Hirose F, Yamaguchi M, Kai M, Oshige M, Sakimoto I, Koiwai O, Sakaguchi K. Drosophila mitochondrial transcription factor A: characterization of its cDNA and expression pattern during development. Biochem Biophys Res Commun 287(2):474-483, 9/21/2001. PMID: 11554753.
22. Oshige M, Yoshida H, Hirose F, Takata KI, Inoue Y, Aoyagi N, Yamaguchi M, Koiwai O, Matsukage A, Sakaguchi K. Molecular cloning and expression during development of the Drosophila gene for the catalytic subunit of DNA polymerase epsilon. Gene 256(1-2):93-100, 10/3/2000. PMID: 11054539.

Invited Articles

1. Lange SS, Takata K, Wood RD. DNA polymerases and cancer. Nat Rev Cancer 11(2):96-110, 2/2011. PMCID: PMC3739438.
2. Takata K, Wood RD. Bypass specialists operate together. EMBO J 28(4):313-4, 2/18/2009. PMCID: PMC2646159.
Other Articles
1. Matsuura S, Naito H, Takata K, Mizushina Y, Murakami Y, Sakaguchi K, Katsura S and Mizuno A. Novel immobilization technique of single-stranded DNA molecules on a glass surface for direct analysis of DNA polymerase activity. Biomolecular Chem:322-325, 12/2003.
2. Takata K and Sakaguchi K. The role of DDB1 in development. Experimental Medicine: Yodosha (Japan) 21:1338-1346, 7/2003.

Last updated: 12/16/2014