Structural basis for molecular interactions in DNA damage tolerance
| Project/Area Number |
25291017
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Partial Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Structural biochemistry
|
|---|
| Research Institution | University of Shizuoka |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
|
|---|
| Keywords | X線結晶構造解析 / 構造生物学 / DNA修復 / DNA損傷 |
|---|
| Outline of Final Research Achievements |
DNA damage occurs both naturally and artificially. Damaged template DNA blocks accurate and processive DNA synthesis by replicative DNA polymerases, resulting in genomic instability which causes various diseases including cancer. To avoid replication arrest and to restart DNA synthesis, cells initiate DNA damage tolerance (DDT). DDT is divided into two pathways, translesion DNA synthesis (TLS) and template-switched DNA synthesis (TS). TLS is transient DNA synthesis using a damaged template by error-prone DNA polymerases specialized for DNA damage. TS, in which one newly synthesized strand is utilized as an undamaged template for replication by replicative polymerases, is an error-free process. In this study, we performed structural analyses by x-ray crystallography and structure-based functional analyses of proteins involved in DDT, thereby clarifying the structural basis for molecular interactions in DDT. Our results could provide a clue to develop novel drugs for cancer therapy.
|
Report
(4 results)
Research Products
(29 results)
-
-
[Journal Article] Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis2016
Author(s)
Tsuyoshi Yamamoto, Yuta Tsunematsu, Kodai Hara, Tomohiro Suzuki, Shinji Kishimoto, Hirokazu Kawaguchi, Hiroshi Noguchi, Hiroshi Hashimoto, Yi Tang, Kinya Hotta, & Kenji Watanabe
-
Journal Title
Angew Chem Int Ed Engl
Volume: 印刷中
Issue: 21
Pages: 6207-6210
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
[Journal Article] A Small Molecule Inhibitor of Monoubiquitinated Proliferating Cell Nuclear Antigen (PCNA) inhibits Repair of Interstrand DNA Crosslink, enhances DNA Double-strand Break, and sensitizes Cancer Cells to Cisplatin2014
Author(s)
Akira Inoue, Sotaro Kikuchi, Asami Hishiki, Youming Shao, Richard Heath, Benjamin J. Evison, Marcelo Actis, Christine E. Canman, Hiroshi Hashimoto, & Naoaki Fujii
-
Journal Title
J. Biol. Chem
Volume: 289
Issue: 10
Pages: 7109-7120
DOI
Related Report
Peer Reviewed
-
[Journal Article] A Missense Mutation in Rev7 Disrupts Formation of Polζ, Impairing Mouse Development and Repair of Genotoxic Agent-induced DNA Lesions2014
Author(s)
Maryam Khalaj, Abdolrahim Abbasi, Hiroshi Yamanishi, Kouyou Akiyama, Shuso Wakitani, Sotaro Kikuchi, Michiko Hirose, Misako Yuzuriha, Masaki Magari, Heba A Degheidy, Kuniya Abe, Atsuo Ogura, Hiroshi Hashimoto, & Tetsuo Kunieda
-
Journal Title
J Biol Chem
Volume: 289
Issue: 6
Pages: 3811-3824
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
