Targeting of the Fun30 nucleosome remodeller by the Dpb11 scaffold facilitates cell cycle-regulated DNA end resection

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Abstract

DNA double strand breaks (DSBs) can be repaired by either recombination-based or direct ligation-based mechanisms. Pathway choice is made at the level of DNA end resection, a nucleolytic processing step, which primes DSBs for repair by recombination. Resection is thus under cell cycle control, but additionally regulated by chromatin and nucleosome remodellers. Here we show that both layers of control converge in the regulation of resection by the evolutionarily conserved Fun30/SMARCAD1 remodeller. Yeast Fun30 and human SMARCAD1 are cell cycle-regulated by interaction with the DSB-localized scaffold proteins Dpb11 and TOPBP1, respectively. In yeast this protein assembly additionally comprises the 9-1-1 damage sensor, is involved in localizing Fun30 to damaged chromatin and thus is required for efficient long-range resection of DSBs. Notably, artificial targeting of Fun30 to DSBs is sufficient to bypass the cell cycle regulation of long-range resection, indicating that chromatin remodelling during resection is underlying DSB repair pathway choice.

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Susanne CS Bantele

DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, Martinsried, Germany

Competing interests
The authors declare that no competing interests exist.
Pedro Ferreira

Centre for Medical Biotechnology, University Duisburg-Essen, Essen, Germany

Competing interests
The authors declare that no competing interests exist.
Dalia Gritenaite

DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, Martinsried, Germany

Competing interests
The authors declare that no competing interests exist.
Dominik Boos

Centre for Medical Biotechnology, University Duisburg-Essen, Essen, Germany

Competing interests
The authors declare that no competing interests exist.
Boris Pfander

DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, Martinsried, Germany

For correspondence
bpfander@biochem.mpg.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2180-5054

Funding

Deutsche Forschungsgemeinschaft (Project Grant,PF794/3-1)

Boris Pfander

Max-Planck-Gesellschaft (Grant)

Boris Pfander

Fonds der chemischen Industrie (Fellowship)

Susanne CS Bantele

NRW Rueckkehrerprogramm from the stae of North-Rhine-Westphalia (Grant)

Dominik Boos

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.