| Budget Amount *help |
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
|
|---|
| Research Abstract |
Werner and Bloom syndrome causative genes, WRN and BLM, encode RecQ helicase. In this study, we addressed the cellular functions of WRN and BLM, and the following results were achieved.
1.The function of RECQL1 and RECQL5 that are member of RecQ helicase family, were not known. We have shown that both RECQL1 and RECQL5 have a backup role of BLM in the cell (MCB 2003).
2.The evidence that ATM interacts with BLM and phosphorylates BLM under DNA damaged condition implicated functional relationship between both. However, our analysis of DT40 blm, atm, and blm/atm cells, revealed that there is little genetics interaction between the two (Biochim.Biophys.Acta.2004).
3.It was shown that the (Fanconi anaemia syndrome) FANC complex interacts with BLM. We reported the existence of functional relationship between FANCC and BLM (EMBO J.2005).
4.The analysis of DT40 wrn/xrcc3, wrn/blm, blm/xrcc3, and wrn/blm/xrcc3 mutant cells, revealed that BLM but not WRN belong to homologous recombination repair pathway, which XRCC3 involves (manuscript in preparation).
5.SGS1 is budding yeast homologue of WRN and BLM gene. It is well known Sgs1 and BLM interact with DNA topoisomerase III (Top3). We showed that the ability of Sgs1 to interact with Top3 is essential for damage induced homologous recombination in budding yeast (DNA Repair 2005).
6.WRNIP1 is a novel protein that interacts with WRN. Using yeast genetics, we analyzed budding yeast counterparts of WRN and WRNIP1, SGS1 and MGS1, respectively. The analysis of sgs1-mgs1 double mutant cells revealed the existence of functional relationship between the two (DNA repair,2002). In addition, Mgs1 genetically interacts with replicative DNA polymerase δ (Mol Genet Genomics,2002;Genes to Cells,2004). Finally, it was shown that human WRNIP1 protein is able to directly bind and stimulate human Polδ activities in the test tube (Genes to Cells,2005).
|
