DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
批准号:
8149277
负责人:
ROGER WOODGATE
金额:
$247.63万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
基因组完整性实验室(LGI)的科学家研究突变引入受损DNA的机制。现在已经知道,许多长期参与诱变过程的蛋白质实际上是低保真度的DNA聚合酶,它们可以在称为翻译DNA合成(TLS)的过程中穿过受损的DNA。
英文摘要
Scientists within the Laboratory of Genomic Integrity (LGI) study the mechanisms by which mutations are introduced into damaged DNA. It is now known that many of the proteins long implicated in the mutagenic process are, in fact, low-fidelity DNA polymerases that can traverse damaged DNA in a process termed translesion DNA synthesis (TLS).
Most damage-induced (SOS) mutagenesis in Escherichia coli occurs when DNA polymerase V, activated by a RecA nucleoprotein filament (RecA*), catalyzes TLS. The biological functions of RecA* in homologous recombination and in mediating LexA and UmuD cleavage during the SOS response are well understood. In contrast, the biochemical role of RecA* in pol V-dependent mutagenic TLS remains poorly characterized. Proposals for the role of RecA* in TLS have evolved from positioning UmuD'C on primer/template DNA proximal to a lesion, to a dynamic interaction involving displacement of RecA* filaments on the template by an advancing pol V, to a model in which RecA* need not be located in cis on the template strand being copied, but can instead assemble on a separate ssDNA strand to transactivate pol V for TLS. As part of a collaborative study with Myron Goodman (University of Southern California), we addressed the hitherto enigmatic role of RecA* in polV-dependent SOS mutagenesis. We demonstrated that RecA* transfers a single RecA-ATP stoichiometrically from its DNA 3'-end to free pol V (UmuD'2C) to form an active mutasome (pol VMut) with the composition UmuD'C-RecA-ATP. Pol VMut catalyzes TLS in the absence of RecA* and deactivates rapidly upon dissociation from DNA. Deactivation occurs more slowly in the absence of DNA synthesis, while retaining RecA-ATP in the complex. Reactivation of pol VMut is triggered by replacement of RecA-ATP from RecA*. Thus, the principal role of RecA* in SOS mutagenesis is to transfer RecA-ATP to pol V, so as to generate active mutasomal complex for translesion synthesis.
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DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:10266476
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资助金额:$203.61万
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负责人:ROGER WOODGATE
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依托单位:
Dna Replication, Repair, And Mutagenesis In Eukaryotic A
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批准号:6671878
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资助金额:$0.0万
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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资助金额:$188.65万
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DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:9550317
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项目类别:
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资助金额:$207.5万
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:10908165
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资助金额:$232.54万
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负责人:ROGER WOODGATE
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依托单位:
DNA REPLICATION, REPAIR, AND MUTAGENESIS IN EUKARYOTIC AND PROKARYOTIC CELLS
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批准号:6290230
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负责人:ROGER WOODGATE
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DNA Replication, Repair, and Mutagenesis In Eukaryotic
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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负责人:ROGER WOODGATE
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DNA Replication, Repair, and Mutagenesis In Eukaryotic A
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负责人:ROGER WOODGATE
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DNA Replication, Repair, and Mutagenesis In Eukaryotic A
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:10007490
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项目类别:
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资助金额:$237.54万
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:8553880
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项目类别:
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:10470630
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项目类别:
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资助金额:$205.62万
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:10685189
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项目类别:
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资助金额:$212.04万
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:9150086
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项目类别:
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资助金额:$219.53万
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotic And Prokaryotic Cells
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批准号:8941464
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项目类别:
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负责人:ROGER WOODGATE
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依托单位:
DNA REPLICATION, REPAIR, AND MUTAGENESIS IN EUKARYOTIC AND PROKARYOTIC CELLS
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批准号:6432570
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资助金额:$0.0万
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负责人:ROGER WOODGATE
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依托单位:
DNA Replication, Repair, and Mutagenesis In Eukaryotes
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批准号:6813746
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项目类别:
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资助金额:$0.0万
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负责人:ROGER WOODGATE
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依托单位:
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