Mobile D-loops are a preferred substrate for the Bloom's syndrome helicase
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作者:
Bachrati, Csanad Z.
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机构:Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, England
Bachrati, Csanad Z.
Borts, Rhona H.
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机构:Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, England
Borts, Rhona H.
Hickson, Ian D.
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Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, EnglandUniv Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, England
Hickson, Ian D.
[1
]
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[1] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, England
[2] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England
The Bloom's syndrome helicase, BLM, is a member of the highly conserved RecQ family, and possesses both DNA unwinding and DNA strand annealing activities. BLM also promotes branch migration of Holliday junctions. One role for BLM is to act in conjunction with topoisomerase III alpha to process homologous recombination (HR) intermediates containing a double Holliday junction by a process termed dissolution. However, several lines of evidence suggest that BLM may also act early in one or more of the recombination pathways to eliminate illegitimate or aberrantly paired DNA joint molecules. We have investigated whether BLM can disrupt DNA displacement loops (D-loops), which represent the initial strand invasion step of HR. We show that mobile D-loops created by the RecA recombinase are a highly preferred substrate for BLM with the invading strand being displaced from the duplex. We have identified structural features of the D-loop that determine the efficiency with which BLM promotes D-loop dissociation. We discuss these results in the context of models for the role of BLM as an 'anti-recombinase'.
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Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, EnglandUniv Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, England
Bachrati, CZ
Hickson, ID
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Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, EnglandUniv Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, England
机构:Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
Cheok, CF
Wu, L
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机构:Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
Wu, L
Garcia, PL
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机构:Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
Garcia, PL
Janscak, P
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机构:Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
Janscak, P
Hickson, ID
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Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, EnglandUniv Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
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Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, EnglandUniv Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, England
Bachrati, CZ
Hickson, ID
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Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, EnglandUniv Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DS, England
机构:Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
Cheok, CF
Wu, L
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机构:Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
Wu, L
Garcia, PL
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机构:Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
Garcia, PL
Janscak, P
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机构:Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England
Janscak, P
Hickson, ID
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Univ Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, EnglandUniv Oxford, John Radcliffe Hosp, Canc Res UK Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England