2014 Fiscal Year Final Research Report
RNase H2 is essential for ribonucleotide excision repair during DNA replication
Project/Area Number |
25650028
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Functional biochemistry
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Research Institution | University of Tsukuba |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Keywords | リボヌクレオチド除去修復 / ゲノム安定性 / RNase H2 |
Outline of Final Research Achievements |
RNase H2 is an enzyme capable of cleaving the 5’-phosphodiester bond of single ribonucleotides (rNMPs) embedded in RNA/DNA heteroduplexes. Embryos homozygous for the targeted mutation of Rnaseh2a gene exhibited gross apoptosis and failed to develop beyond E10.5. Chromosomal DNA from mutant embryos contained numerous rNMPs. Expression of DNA damage response genes, including cyclin G1 and p21, was up-regulated by the absence of RNase H2. It was also found that the enzyme is essential for normal cell proliferation via correct chromosomal DNA replication but is dispensable for cell survival. These results indicate that RNase H2 is a key enzyme responsible for eliminating rNMPs misincorporated during DNA replication, thereby ensuring genome stability and normal cell proliferation.
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Free Research Field |
分子細胞生物学
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