Identification of the MMS22L-TONSL Complex that Promotes Homologous Recombination

Eris Duro; Cecilia Lundin; Katrine Ask; Luis Sanchez-Pulido; Thomas J. MacArtney; Rachel Toth; Chris Ponting; Anja Groth; Thomas Helleday; John Rouse

doi:10.1016/j.molcel.2010.10.023

Identification of the MMS22L-TONSL Complex that Promotes Homologous Recombination

Eris Duro, Cecilia Lundin, Katrine Ask, Luis Sanchez-Pulido, Thomas J. MacArtney, Rachel Toth, Chris Ponting, Anja Groth, Thomas Helleday, John Rouse^*

^*Corresponding author for this work

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

Abstract

Budding yeast Mms22 is required for homologous recombination (HR)-mediated repair of stalled or broken DNA replication forks. Here we identify a human Mms22-like protein (MMS22L) and an MMS22L-interacting protein, NF kappa BIL2/TONSL. Depletion of MMS22L or TONSL from human cells causes a high level of double-strand breaks (DSBs) during DNA replication. Both proteins accumulate at stressed replication forks, and depletion of MMS22L or TONSL from cells causes hypersensitivity to agents that cause S phase-associated DSBs, such as topoisomerase (TOP) inhibitors. In this light, MMS22L and TONSL are required for the HR-mediated repair of replication fork-associated DSBs. In cells depleted of either protein, DSBs induced by the TOP1 inhibitor camptothecin are resected normally, but the loading of the RAD51 recombinase is defective. Therefore, MMS22L and TONSL are required for the maintenance of genome stability when unscheduled DSBs occur in the vicinity of DNA replication forks.

Original language	English
Pages (from-to)	632-644
Number of pages	13
Journal	Molecular Cell
Volume	40
Issue number	4
Early online date	4 Nov 2010
DOIs	https://doi.org/10.1016/j.molcel.2010.10.023
Publication status	Published - 24 Nov 2010

Keywords

Amino Acid Sequence
Cell Cycle Proteins
Cell Line
Cell Survival
Computational Biology
DNA Breaks, Double-Stranded
DNA-Binding Proteins
DNA-Directed DNA Polymerase
Drug Resistance
Humans
Models, Biological
Molecular Sequence Data
Multienzyme Complexes
Multiprotein Complexes
NF-kappa B
Nuclear Proteins
Protein Binding
Rad51 Recombinase
Recombination, Genetic
S Phase

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title = "Identification of the MMS22L-TONSL Complex that Promotes Homologous Recombination",

abstract = "Budding yeast Mms22 is required for homologous recombination (HR)-mediated repair of stalled or broken DNA replication forks. Here we identify a human Mms22-like protein (MMS22L) and an MMS22L-interacting protein, NF kappa BIL2/TONSL. Depletion of MMS22L or TONSL from human cells causes a high level of double-strand breaks (DSBs) during DNA replication. Both proteins accumulate at stressed replication forks, and depletion of MMS22L or TONSL from cells causes hypersensitivity to agents that cause S phase-associated DSBs, such as topoisomerase (TOP) inhibitors. In this light, MMS22L and TONSL are required for the HR-mediated repair of replication fork-associated DSBs. In cells depleted of either protein, DSBs induced by the TOP1 inhibitor camptothecin are resected normally, but the loading of the RAD51 recombinase is defective. Therefore, MMS22L and TONSL are required for the maintenance of genome stability when unscheduled DSBs occur in the vicinity of DNA replication forks.",

keywords = "Amino Acid Sequence, Cell Cycle Proteins, Cell Line, Cell Survival, Computational Biology, DNA Breaks, Double-Stranded, DNA-Binding Proteins, DNA-Directed DNA Polymerase, Drug Resistance, Humans, Models, Biological, Molecular Sequence Data, Multienzyme Complexes, Multiprotein Complexes, NF-kappa B, Nuclear Proteins, Protein Binding, Rad51 Recombinase, Recombination, Genetic, S Phase",

author = "Eris Duro and Cecilia Lundin and Katrine Ask and Luis Sanchez-Pulido and MacArtney, {Thomas J.} and Rachel Toth and Chris Ponting and Anja Groth and Thomas Helleday and John Rouse",

year = "2010",

month = nov,

day = "24",

doi = "10.1016/j.molcel.2010.10.023",

language = "English",

volume = "40",

pages = "632--644",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "4",

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TY - JOUR

T1 - Identification of the MMS22L-TONSL Complex that Promotes Homologous Recombination

AU - Duro, Eris

AU - Lundin, Cecilia

AU - Ask, Katrine

AU - Sanchez-Pulido, Luis

AU - MacArtney, Thomas J.

AU - Toth, Rachel

AU - Ponting, Chris

AU - Groth, Anja

AU - Helleday, Thomas

AU - Rouse, John

PY - 2010/11/24

Y1 - 2010/11/24

N2 - Budding yeast Mms22 is required for homologous recombination (HR)-mediated repair of stalled or broken DNA replication forks. Here we identify a human Mms22-like protein (MMS22L) and an MMS22L-interacting protein, NF kappa BIL2/TONSL. Depletion of MMS22L or TONSL from human cells causes a high level of double-strand breaks (DSBs) during DNA replication. Both proteins accumulate at stressed replication forks, and depletion of MMS22L or TONSL from cells causes hypersensitivity to agents that cause S phase-associated DSBs, such as topoisomerase (TOP) inhibitors. In this light, MMS22L and TONSL are required for the HR-mediated repair of replication fork-associated DSBs. In cells depleted of either protein, DSBs induced by the TOP1 inhibitor camptothecin are resected normally, but the loading of the RAD51 recombinase is defective. Therefore, MMS22L and TONSL are required for the maintenance of genome stability when unscheduled DSBs occur in the vicinity of DNA replication forks.

AB - Budding yeast Mms22 is required for homologous recombination (HR)-mediated repair of stalled or broken DNA replication forks. Here we identify a human Mms22-like protein (MMS22L) and an MMS22L-interacting protein, NF kappa BIL2/TONSL. Depletion of MMS22L or TONSL from human cells causes a high level of double-strand breaks (DSBs) during DNA replication. Both proteins accumulate at stressed replication forks, and depletion of MMS22L or TONSL from cells causes hypersensitivity to agents that cause S phase-associated DSBs, such as topoisomerase (TOP) inhibitors. In this light, MMS22L and TONSL are required for the HR-mediated repair of replication fork-associated DSBs. In cells depleted of either protein, DSBs induced by the TOP1 inhibitor camptothecin are resected normally, but the loading of the RAD51 recombinase is defective. Therefore, MMS22L and TONSL are required for the maintenance of genome stability when unscheduled DSBs occur in the vicinity of DNA replication forks.

KW - Amino Acid Sequence

KW - Cell Cycle Proteins

KW - Cell Line

KW - Cell Survival

KW - Computational Biology

KW - DNA Breaks, Double-Stranded

KW - DNA-Binding Proteins

KW - DNA-Directed DNA Polymerase

KW - Drug Resistance

KW - Humans

KW - Models, Biological

KW - Molecular Sequence Data

KW - Multienzyme Complexes

KW - Multiprotein Complexes

KW - NF-kappa B

KW - Nuclear Proteins

KW - Protein Binding

KW - Rad51 Recombinase

KW - Recombination, Genetic

KW - S Phase

U2 - 10.1016/j.molcel.2010.10.023

DO - 10.1016/j.molcel.2010.10.023

M3 - Article

C2 - 21055984

VL - 40

SP - 632

EP - 644

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 4

ER -

Identification of the MMS22L-TONSL Complex that Promotes Homologous Recombination

Abstract

Keywords

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