| 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)
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| 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.
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