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PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination

by Issaeva, Natalia , Loseva, Olga , Schultz, Niklas , Fernandez, Serena , Bryant, Helen E , Jemth, Ann‐Sofie , Helleday, Thomas , Petermann, Eva , Johansson, Fredrik , McGlynn, Peter

in Adenosine diphosphate / Animals / Biomedical research / Cell cycle / Cell Cycle Proteins - metabolism / Cells, Cultured / Cricetinae / Cricetulus / Deoxyribonucleic acid / DNA / DNA Repair / DNA Replication - physiology / DNA-Binding Proteins - metabolism / EMBO06 / EMBO13 / Fluorescent Antibody Technique / Genetic recombination / homologous recombination / Molecular biology / Mre11 / poly(ADP-ribose) polymerase / Poly(ADP-ribose) Polymerases - metabolism / Recombination, Genetic - physiology / replication restart / stalled replication forks

2009

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PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination

by Issaeva, Natalia , Loseva, Olga , Schultz, Niklas , Fernandez, Serena , Bryant, Helen E , Jemth, Ann‐Sofie , Helleday, Thomas , Petermann, Eva , Johansson, Fredrik , McGlynn, Peter

2009

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PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination

by Issaeva, Natalia , Loseva, Olga , Schultz, Niklas , Fernandez, Serena , Bryant, Helen E , Jemth, Ann‐Sofie , Helleday, Thomas , Petermann, Eva , Johansson, Fredrik , McGlynn, Peter

2009

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Journal Article

PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination

Issaeva, Natalia,

Loseva, Olga,

Schultz, Niklas,

Fernandez, Serena,

Bryant, Helen E,

Jemth, Ann‐Sofie,

Helleday, Thomas,

Petermann, Eva,

Johansson, Fredrik,

McGlynn, Peter

2009

Overview

If replication forks are perturbed, a multifaceted response including several DNA repair and cell cycle checkpoint pathways is activated to ensure faithful DNA replication. Here, we show that poly(ADP‐ribose) polymerase 1 (PARP1) binds to and is activated by stalled replication forks that contain small gaps. PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA. Both PARP1 and PARP2 are required for hydroxyurea‐induced homologous recombination to promote cell survival after replication blocks. Together, our data suggest that PARP1 and PARP2 detect disrupted replication forks and attract Mre11 for end processing that is required for subsequent recombination repair and restart of replication forks.

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Publisher

John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group

Subject

Adenosine diphosphate

/ Animals

/ Biomedical research

/ Cell cycle

/ Cell Cycle Proteins - metabolism

/ Cells, Cultured

/ Cricetinae