Processing of DNA structures via DNA unwinding and branch migration by the S. cerevisiae Mph1 protein

Xiao Feng Zheng; Rohit Prakash; Dorina Saro; Simonne Longerich; Hengyao Niu; Patrick Sung

doi:10.1016/j.dnarep.2011.08.002

Processing of DNA structures via DNA unwinding and branch migration by the S. cerevisiae Mph1 protein

Xiao Feng Zheng, Rohit Prakash, Dorina Saro, Simonne Longerich, Hengyao Niu, Patrick Sung

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

The budding yeast Mph1 protein, the putative ortholog of human FANCM, possesses a 3' to 5' DNA helicase activity and is capable of disrupting the D-loop structure to suppress chromosome arm crossovers in mitotic homologous recombination. Similar to FANCM, genetic studies have implicated Mph1 in DNA replication fork repair. Consistent with this genetic finding, we show here that Mph1 is able to mediate replication fork reversal, and to process the Holliday junction via DNA branch migration. Moreover, Mph1 unwinds 3' and 5' DNA Flap structures that bear key features of the D-loop. These biochemical results not only provide validation for a role of Mph1 in the repair of damaged replication forks, but they also offer mechanistic insights as to its ability to efficiently disrupt the D-loop intermediate.

Original language	English (US)
Pages (from-to)	1034-1043
Number of pages	10
Journal	DNA Repair
Volume	10
Issue number	10
DOIs	https://doi.org/10.1016/j.dnarep.2011.08.002
State	Published - Oct 10 2011
Externally published	Yes

Keywords

Branch migration
D-loop
Fork regression
Helicase
Mph1
Recombination
Replication fork

ASJC Scopus subject areas

Molecular Biology
Biochemistry
Cell Biology

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10.1016/j.dnarep.2011.08.002

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title = "Processing of DNA structures via DNA unwinding and branch migration by the S. cerevisiae Mph1 protein",

abstract = "The budding yeast Mph1 protein, the putative ortholog of human FANCM, possesses a 3' to 5' DNA helicase activity and is capable of disrupting the D-loop structure to suppress chromosome arm crossovers in mitotic homologous recombination. Similar to FANCM, genetic studies have implicated Mph1 in DNA replication fork repair. Consistent with this genetic finding, we show here that Mph1 is able to mediate replication fork reversal, and to process the Holliday junction via DNA branch migration. Moreover, Mph1 unwinds 3' and 5' DNA Flap structures that bear key features of the D-loop. These biochemical results not only provide validation for a role of Mph1 in the repair of damaged replication forks, but they also offer mechanistic insights as to its ability to efficiently disrupt the D-loop intermediate.",

keywords = "Branch migration, D-loop, Fork regression, Helicase, Mph1, Recombination, Replication fork",

author = "Zheng, {Xiao Feng} and Rohit Prakash and Dorina Saro and Simonne Longerich and Hengyao Niu and Patrick Sung",

note = "Funding Information: We are grateful to Leonard Wu (University of Oxford, UK) for providing plasmids pG46 and pG68 and for his advice in substrate preparation. We thank Sierra Colavito for providing the Srs2 protein. This study was supported by NIH grants RO1 ES015632 , RO1 ES07061 and RO1 GM57814 . ",

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doi = "10.1016/j.dnarep.2011.08.002",

language = "English (US)",

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T1 - Processing of DNA structures via DNA unwinding and branch migration by the S. cerevisiae Mph1 protein

AU - Zheng, Xiao Feng

AU - Prakash, Rohit

AU - Saro, Dorina

AU - Longerich, Simonne

AU - Niu, Hengyao

AU - Sung, Patrick

N1 - Funding Information: We are grateful to Leonard Wu (University of Oxford, UK) for providing plasmids pG46 and pG68 and for his advice in substrate preparation. We thank Sierra Colavito for providing the Srs2 protein. This study was supported by NIH grants RO1 ES015632 , RO1 ES07061 and RO1 GM57814 .

PY - 2011/10/10

Y1 - 2011/10/10

N2 - The budding yeast Mph1 protein, the putative ortholog of human FANCM, possesses a 3' to 5' DNA helicase activity and is capable of disrupting the D-loop structure to suppress chromosome arm crossovers in mitotic homologous recombination. Similar to FANCM, genetic studies have implicated Mph1 in DNA replication fork repair. Consistent with this genetic finding, we show here that Mph1 is able to mediate replication fork reversal, and to process the Holliday junction via DNA branch migration. Moreover, Mph1 unwinds 3' and 5' DNA Flap structures that bear key features of the D-loop. These biochemical results not only provide validation for a role of Mph1 in the repair of damaged replication forks, but they also offer mechanistic insights as to its ability to efficiently disrupt the D-loop intermediate.

AB - The budding yeast Mph1 protein, the putative ortholog of human FANCM, possesses a 3' to 5' DNA helicase activity and is capable of disrupting the D-loop structure to suppress chromosome arm crossovers in mitotic homologous recombination. Similar to FANCM, genetic studies have implicated Mph1 in DNA replication fork repair. Consistent with this genetic finding, we show here that Mph1 is able to mediate replication fork reversal, and to process the Holliday junction via DNA branch migration. Moreover, Mph1 unwinds 3' and 5' DNA Flap structures that bear key features of the D-loop. These biochemical results not only provide validation for a role of Mph1 in the repair of damaged replication forks, but they also offer mechanistic insights as to its ability to efficiently disrupt the D-loop intermediate.

KW - Branch migration

KW - D-loop

KW - Fork regression

KW - Helicase

KW - Mph1

KW - Recombination

KW - Replication fork

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Processing of DNA structures via DNA unwinding and branch migration by the S. cerevisiae Mph1 protein

Abstract

Keywords

ASJC Scopus subject areas

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