Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

Sonia Cristina Pinela da Silva; Veronika Altmannova; Sarah Luke-Glaser; Peter Henriksen; Irene Gallina; Xuejiao Yang; Chuna Ram Choudhary; Brian Luke; Lumir Krejci; Michael Lisby

doi:10.1101/gad.276204.115

Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

Sonia Cristina Pinela da Silva, Veronika Altmannova, Sarah Luke-Glaser, Peter Henriksen, Irene Gallina, Xuejiao Yang, Chuna Ram Choudhary, Brian Luke, Lumir Krejci, Michael Lisby

19 Citations (Scopus)

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Abstract

Mph1 is a member of the conserved FANCM family of DNA motor proteins that play key roles in genome maintenance processes underlying Fanconi anemia, a cancer predisposition syndrome in humans. Here, we identify Mte1 as a novel interactor of the Mph1 helicase in Saccharomyces cerevisiae. In vitro, Mte1 (Mph1-associated telomere maintenance protein 1) binds directly to DNA with a preference for branched molecules such as D loops and fork structures. In addition, Mte1 stimulates the helicase and fork regression activities of Mph1 while inhibiting the ability of Mph1 to dissociate recombination intermediates. Deletion of MTE1 reduces crossover recombination and suppresses the sensitivity of mph1Δ mutant cells to replication stress. Mph1 and Mte1 interdependently colocalize atDNAdamage-induced foci and dysfunctional telomeres, and MTE1 deletion results in elongated telomeres. Taken together, our data indicate that Mte1 plays a role in regulation of crossover recombination, response to replication stress, and telomere maintenance.

Original language	English
Journal	Genes & Development
Volume	30
Issue number	6
Pages (from-to)	700-717
Number of pages	18
ISSN	0890-9369
DOIs	https://doi.org/10.1101/gad.276204.115
Publication status	Published - 15 Mar 2016

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title = "Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance",

abstract = "Mph1 is a member of the conserved FANCM family of DNA motor proteins that play key roles in genome maintenance processes underlying Fanconi anemia, a cancer predisposition syndrome in humans. Here, we identify Mte1 as a novel interactor of the Mph1 helicase in Saccharomyces cerevisiae. In vitro, Mte1 (Mph1-associated telomere maintenance protein 1) binds directly to DNA with a preference for branched molecules such as D loops and fork structures. In addition, Mte1 stimulates the helicase and fork regression activities of Mph1 while inhibiting the ability of Mph1 to dissociate recombination intermediates. Deletion of MTE1 reduces crossover recombination and suppresses the sensitivity of mph1Δ mutant cells to replication stress. Mph1 and Mte1 interdependently colocalize atDNAdamage-induced foci and dysfunctional telomeres, and MTE1 deletion results in elongated telomeres. Taken together, our data indicate that Mte1 plays a role in regulation of crossover recombination, response to replication stress, and telomere maintenance.",

author = "{Pinela da Silva}, {Sonia Cristina} and Veronika Altmannova and Sarah Luke-Glaser and Peter Henriksen and Irene Gallina and Xuejiao Yang and Choudhary, {Chuna Ram} and Brian Luke and Lumir Krejci and Michael Lisby",

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T1 - Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

AU - Pinela da Silva, Sonia Cristina

AU - Altmannova, Veronika

AU - Luke-Glaser, Sarah

AU - Henriksen, Peter

AU - Gallina, Irene

AU - Yang, Xuejiao

AU - Choudhary, Chuna Ram

AU - Luke, Brian

AU - Krejci, Lumir

AU - Lisby, Michael

PY - 2016/3/15

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N2 - Mph1 is a member of the conserved FANCM family of DNA motor proteins that play key roles in genome maintenance processes underlying Fanconi anemia, a cancer predisposition syndrome in humans. Here, we identify Mte1 as a novel interactor of the Mph1 helicase in Saccharomyces cerevisiae. In vitro, Mte1 (Mph1-associated telomere maintenance protein 1) binds directly to DNA with a preference for branched molecules such as D loops and fork structures. In addition, Mte1 stimulates the helicase and fork regression activities of Mph1 while inhibiting the ability of Mph1 to dissociate recombination intermediates. Deletion of MTE1 reduces crossover recombination and suppresses the sensitivity of mph1Δ mutant cells to replication stress. Mph1 and Mte1 interdependently colocalize atDNAdamage-induced foci and dysfunctional telomeres, and MTE1 deletion results in elongated telomeres. Taken together, our data indicate that Mte1 plays a role in regulation of crossover recombination, response to replication stress, and telomere maintenance.

AB - Mph1 is a member of the conserved FANCM family of DNA motor proteins that play key roles in genome maintenance processes underlying Fanconi anemia, a cancer predisposition syndrome in humans. Here, we identify Mte1 as a novel interactor of the Mph1 helicase in Saccharomyces cerevisiae. In vitro, Mte1 (Mph1-associated telomere maintenance protein 1) binds directly to DNA with a preference for branched molecules such as D loops and fork structures. In addition, Mte1 stimulates the helicase and fork regression activities of Mph1 while inhibiting the ability of Mph1 to dissociate recombination intermediates. Deletion of MTE1 reduces crossover recombination and suppresses the sensitivity of mph1Δ mutant cells to replication stress. Mph1 and Mte1 interdependently colocalize atDNAdamage-induced foci and dysfunctional telomeres, and MTE1 deletion results in elongated telomeres. Taken together, our data indicate that Mte1 plays a role in regulation of crossover recombination, response to replication stress, and telomere maintenance.

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DO - 10.1101/gad.276204.115

M3 - Journal article

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SN - 0890-9369

VL - 30

SP - 700

EP - 717

JO - Genes & Development

JF - Genes & Development

IS - 6

ER -

Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

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