Sugasawa Group: Cross-regulation of the maintenance and mutagenesis of genomic sequence and epigenetic information
|Principal Investigator||Kaoru Sugasawa
Biosignal Research Center, Kobe University
DNA is constantly damaged by various assaults, both from the environment and the cell’s own energy metabolism. Repair of damaged DNA is affected by local epigenetic environment, but at the same time, DNA repair mechanisms can disturb or rewrite existing epigenetic information. Many of the details of the molecular mechanisms underlying DNA repair have yet to be explored. In this project, we will investigate the molecular basis of the cross-regulation between the DNA repair mechanisms that maintain genomic sequence information and the molecular mechanisms involved in the maintenance and reorganization of epigenetic information. We will also investigate the causal relationship between genomic instability and epigenetic abnormality that are resulting from the failure of the cross-regulation and the mechanisms underlying the onset of various diseases and morbid conditions. Particularly, this study seeks to provide answers to the following questions:
- How does epigenetic information already written at the damaged site affect mechanisms of repair of damage to DNA bases, such as the base excision repair (BER) and nucleotide excision repair (NER)? What changes in the epigenetic environment are needed to implement the repair process?
- What roles do DNA damage and its repair mechanisms play in the maintenance and reorganization of epigenetic information? What abnormalities can be caused by failures in DNA repair?
- Fischer, ES., Scrima, A., Böhm, K., Matsumoto, S., Lingaraju, GM., Faty, M., Yasuda, T., Cavadini, S., Wakasugi, M., Hanaoka, F., Iwai, S., Gut, H., Sugasawa, K., and *Thomä, NH.
The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation.
Cell 147, 1024-1039 (2011)
- Yanagihara, H., Kobayashi, J., Tateishi, S., Kato, A., Matsuura, S., Tauchi, H., Yamada, K., Takezawa, J., Sugasawa, K., Masutani, C., Hanaoka, F., Weemaes, CM., and Mori, T., Zou, L., and *Komatsu, K.
NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol η-dependent translesion DNA synthesis.
Mol. Cell 43, 788-797 (2011)
- Yanagihara, H., Kobayashi, J., Tateishi, S., Kato, A., Matsuura, S., Tauchi, H., Yamada, K., Takezawa, J., Sugasawa, K., Masutani, C., Hanaoka, F., Weemaes, CM., Mori, T., Zou, L., and *Komatsu, K.
NBS1 recruits RAD18 via a RAD6-like motif and regulates Pol h-dependent translesion DNA synthesis.
Mol. Cell 43, 788-797 (2011)
- Shimizu, Y., Uchimura, Y., Dohmae, N., Saitoh, H., Hanaoka, F., and *Sugasawa, K.
Stimulation of DNA glycosylase activities by XPC protein complex: roles of protein-protein interactions.
J Nucleic Acids 2010, pii 805698 (2010)
- *Sugasawa, K., Akagi, J., Nishi, R., Iwai, S., and Hanaoka, F.
Two-step recognition of DNA damage for mammalian nucleotide excision repair: directional binding of the XPC complex and DNA strand scanning.
Mol. Cell 36, 642-653 (2009)
- Nishi, R., Alekseev, S., Dinant, C., Hoogstraten, D., Houtsmuller, AB., Hoeijmakers, JHJ., Vermeulen, W., Hanaoka, F., and *Sugasawa, K.
UV-DDB-dependent regulation of nucleotide excision repair kinetics in living cells.
DNA Repair (Amst.) 8, 767-776 (2009)
- *Sugasawa, K.
Xeroderma pigmentosum genes: functions inside and outside DNA repair.
Carcinogenesis 29, 455-465 [review] (2008)
- Yasuda, G., Nishi, R., Watanabe, E., Mori, T., Iwai, S., Orioli, D., Stefanini, M., Hanaoka, F., and *Sugasawa, K.
In vivo destabilization and functional defects of the xeroderma pigmentosum C protein caused by a pathogenic missense mutation.
Mol. Cell. Biol. 27, 6606-6614 (2007)
- *Sugasawa, K.
UV-induced ubiquitylation of XPC complex, the UV-DDB-ubiquitin ligase complex, and DNA repair.
J. Mol. Histol. 37, 189- 202 [review] (2006)
- Baba, D., Maita, N., Jee, J-G., Uchimura, Y., Saitoh, H., Sugasawa, K., Hanaoka, F., Tochio, H., Hiroaki, H., and *Shirakawa, M.
Crystal structure of thymine- DNA glycosylase conjugated to SUMO-1.
Nature 435, 979-982 (2005)
- *Sugasawa, K., Okuda, Y., Saijo, M., Nishi, R., Matsuda, N., Chu, G., Mori, T., Iwai, S., Tanaka, K., Tanaka, K., and Hanaoka, F.
UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex.
Cell 121, 387-400 (2005)
- Shimizu, Y., Iwai, S., Hanaoka, F., and *Sugasawa, K.
Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase.
EMBO J. 22, 164-173 (2003)