2012 Fiscal Year Final Research Report
Why are microsatellites unstable?
| Project/Area Number |
22570010
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Genetics/Genome dynamics
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| Research Institution | National Hospital Organization, Kyushu Cancer Center |
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Principal Investigator |
ODA Shinya 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他の部局等 (40333372)
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| Co-Investigator(Renkei-kenkyūsha) |
KURAOKA Isao 大阪大学, 大学院・基礎工学研究科, 准教授 (60335396)
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| Project Period (FY) |
2010 – 2012
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| Keywords | ゲノム構築・再編・維持 / ゲノム不安定性 / 癌 / DNA 修復 |
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| Research Abstract |
This study aimed to understand the molecular mechanisms that underlie the diversity of microsatellites in human populations and the instability of those in the pathological conditions, particularly, in tumour cells, and, consequently, to elucidate the bona fide dynamics of microsatellites and its pathogenic significance in higher eukaryotic organisms. First, we observed the extreme paucity of polymorphisms in mononucleotide microsatellites among human populations, which makes a remarkable contrast to the dinucleotide microsatellite dynamics. We next analysed mononucleotide and dinucleotide microsatellite alterations under various genetic backgrounds and, consequently, found that the dynamics of these two categories of microsatellites are distinctive depending on the defects in DNA mismatch repair (MMR) and DNA polymerase proofreading (PPR). Analyses using mouse embryo fibroblasts lacking both MMR and PPR are now underway.
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