Novel RNA and DNA strand exchange activity of the PALB2 DNA binding domain and its critical role for DNA repair in cells

Jaigeeth Deveryshetty; Thibaut Peterlini; Mikhail Ryzhikov; Nadine Brahiti; Graham Dellaire; Jean Yves Masson; Sergey Korolev

doi:10.7554/eLife.44063

Novel RNA and DNA strand exchange activity of the PALB2 DNA binding domain and its critical role for DNA repair in cells

Jaigeeth Deveryshetty, Thibaut Peterlini, Mikhail Ryzhikov, Nadine Brahiti, Graham Dellaire, Jean Yves Masson, Sergey Korolev

Résultat de recherche: Article › examen par les pairs

17 Citations (Scopus)

Résumé

BReast Cancer Associated proteins 1 and 2 (BRCA1, -2) and Partner and Localizer of BRCA2 (PALB2) protein are tumour suppressors linked to a spectrum of malignancies, including breast cancer and Fanconi anemia. PALB2 coordinates functions of BRCA1 and BRCA2 during homology-directed repair (HDR) and interacts with several chromatin proteins. In addition to protein scaffold function, PALB2 binds DNA. The functional role of this interaction is poorly understood. We identified a major DNA-binding site of PALB2, mutations in which reduce RAD51 foci formation and the overall HDR efficiency in cells by 50%. PALB2 N-terminal DNA-binding domain (N-DBD) stimulates the function of RAD51 recombinase. Surprisingly, it possesses the strand exchange activity without RAD51. Moreover, N-DBD stimulates the inverse strand exchange and can use DNA and RNA substrates. Our data reveal a versatile DNA interaction property of PALB2 and demonstrate a critical role of PALB2 DNA binding for chromosome repair in cells.

Langue d'origine	English
Numéro d'article	e44063
Journal	eLife
Volume	8
DOI	https://doi.org/10.7554/eLife.44063
Statut de publication	Published - avr. 2019

Note bibliographique

Funding Information:
We are grateful to the members of Korolev lab including Ian Miller for help with cloning, Lakshmi Kanikkannan and Jennifer Redington for help with protein purification and DNA-binding assays. We are grateful to Drs Alessandro Vindigni and Joel Eissenberg for the manuscript evaluation and discussions. We thank Amélie Rodrigue and Yan Coulombe from the Masson lab for technical support. J-YM is a FRQS Chair in genome stability. The research was supported by Siteman Cancer Center (SCC) and the Foundation for Barnes-Jewish Hospital Siteman Investment Program (SIP) [Pre-R01 award to SK]; the Canadian Institutes of Health Research (GD); and a Canadian Institutes of Health Research Foundation grant to J-YM Funding for open access charge: National Institute of Health.

Funding Information:
We are grateful to the members of Korolev lab including Ian Miller for help with cloning, Lakshmi Kanikkannan and Jennifer Redington for help with protein purification and DNA-binding assays. We are grateful to Drs Alessandro Vindigni and Joel Eissenberg for the manuscript evaluation and discussions. We thank Amelie Rodrigue and Yan Coulombe from the Masson lab for technical support. J-YM is a FRQS Chair in genome stability. The research was supported by Siteman Cancer Center (SCC) and the Foundation for Barnes-Jewish Hospital Siteman Investment Program (SIP) [Pre-R01 award to SK]; the Canadian Institutes of Health Research (GD); and a Canadian Institutes of Health Research Foundation grant to J-YM Funding for open access charge: National Institute of Health.

Publisher Copyright:
© 2019, eLife Sciences Publications Ltd. All rights reserved.

ASJC Scopus Subject Areas

General Neuroscience
General Biochemistry,Genetics and Molecular Biology
General Immunology and Microbiology

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Cette action contribue à la réalisation des objectifs de développement durable suivants

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10.7554/eLife.44063

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title = "Novel RNA and DNA strand exchange activity of the PALB2 DNA binding domain and its critical role for DNA repair in cells",

abstract = "BReast Cancer Associated proteins 1 and 2 (BRCA1, -2) and Partner and Localizer of BRCA2 (PALB2) protein are tumour suppressors linked to a spectrum of malignancies, including breast cancer and Fanconi anemia. PALB2 coordinates functions of BRCA1 and BRCA2 during homology-directed repair (HDR) and interacts with several chromatin proteins. In addition to protein scaffold function, PALB2 binds DNA. The functional role of this interaction is poorly understood. We identified a major DNA-binding site of PALB2, mutations in which reduce RAD51 foci formation and the overall HDR efficiency in cells by 50%. PALB2 N-terminal DNA-binding domain (N-DBD) stimulates the function of RAD51 recombinase. Surprisingly, it possesses the strand exchange activity without RAD51. Moreover, N-DBD stimulates the inverse strand exchange and can use DNA and RNA substrates. Our data reveal a versatile DNA interaction property of PALB2 and demonstrate a critical role of PALB2 DNA binding for chromosome repair in cells.",

author = "Jaigeeth Deveryshetty and Thibaut Peterlini and Mikhail Ryzhikov and Nadine Brahiti and Graham Dellaire and Masson, {Jean Yves} and Sergey Korolev",

note = "Funding Information: We are grateful to the members of Korolev lab including Ian Miller for help with cloning, Lakshmi Kanikkannan and Jennifer Redington for help with protein purification and DNA-binding assays. We are grateful to Drs Alessandro Vindigni and Joel Eissenberg for the manuscript evaluation and discussions. We thank Am{\'e}lie Rodrigue and Yan Coulombe from the Masson lab for technical support. J-YM is a FRQS Chair in genome stability. The research was supported by Siteman Cancer Center (SCC) and the Foundation for Barnes-Jewish Hospital Siteman Investment Program (SIP) [Pre-R01 award to SK]; the Canadian Institutes of Health Research (GD); and a Canadian Institutes of Health Research Foundation grant to J-YM Funding for open access charge: National Institute of Health. Funding Information: We are grateful to the members of Korolev lab including Ian Miller for help with cloning, Lakshmi Kanikkannan and Jennifer Redington for help with protein purification and DNA-binding assays. We are grateful to Drs Alessandro Vindigni and Joel Eissenberg for the manuscript evaluation and discussions. We thank Amelie Rodrigue and Yan Coulombe from the Masson lab for technical support. J-YM is a FRQS Chair in genome stability. The research was supported by Siteman Cancer Center (SCC) and the Foundation for Barnes-Jewish Hospital Siteman Investment Program (SIP) [Pre-R01 award to SK]; the Canadian Institutes of Health Research (GD); and a Canadian Institutes of Health Research Foundation grant to J-YM Funding for open access charge: National Institute of Health. Publisher Copyright: {\textcopyright} 2019, eLife Sciences Publications Ltd. All rights reserved.",

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AU - Brahiti, Nadine

AU - Dellaire, Graham

AU - Masson, Jean Yves

AU - Korolev, Sergey

N1 - Funding Information: We are grateful to the members of Korolev lab including Ian Miller for help with cloning, Lakshmi Kanikkannan and Jennifer Redington for help with protein purification and DNA-binding assays. We are grateful to Drs Alessandro Vindigni and Joel Eissenberg for the manuscript evaluation and discussions. We thank Amélie Rodrigue and Yan Coulombe from the Masson lab for technical support. J-YM is a FRQS Chair in genome stability. The research was supported by Siteman Cancer Center (SCC) and the Foundation for Barnes-Jewish Hospital Siteman Investment Program (SIP) [Pre-R01 award to SK]; the Canadian Institutes of Health Research (GD); and a Canadian Institutes of Health Research Foundation grant to J-YM Funding for open access charge: National Institute of Health. Funding Information: We are grateful to the members of Korolev lab including Ian Miller for help with cloning, Lakshmi Kanikkannan and Jennifer Redington for help with protein purification and DNA-binding assays. We are grateful to Drs Alessandro Vindigni and Joel Eissenberg for the manuscript evaluation and discussions. We thank Amelie Rodrigue and Yan Coulombe from the Masson lab for technical support. J-YM is a FRQS Chair in genome stability. The research was supported by Siteman Cancer Center (SCC) and the Foundation for Barnes-Jewish Hospital Siteman Investment Program (SIP) [Pre-R01 award to SK]; the Canadian Institutes of Health Research (GD); and a Canadian Institutes of Health Research Foundation grant to J-YM Funding for open access charge: National Institute of Health. Publisher Copyright: © 2019, eLife Sciences Publications Ltd. All rights reserved.

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N2 - BReast Cancer Associated proteins 1 and 2 (BRCA1, -2) and Partner and Localizer of BRCA2 (PALB2) protein are tumour suppressors linked to a spectrum of malignancies, including breast cancer and Fanconi anemia. PALB2 coordinates functions of BRCA1 and BRCA2 during homology-directed repair (HDR) and interacts with several chromatin proteins. In addition to protein scaffold function, PALB2 binds DNA. The functional role of this interaction is poorly understood. We identified a major DNA-binding site of PALB2, mutations in which reduce RAD51 foci formation and the overall HDR efficiency in cells by 50%. PALB2 N-terminal DNA-binding domain (N-DBD) stimulates the function of RAD51 recombinase. Surprisingly, it possesses the strand exchange activity without RAD51. Moreover, N-DBD stimulates the inverse strand exchange and can use DNA and RNA substrates. Our data reveal a versatile DNA interaction property of PALB2 and demonstrate a critical role of PALB2 DNA binding for chromosome repair in cells.

AB - BReast Cancer Associated proteins 1 and 2 (BRCA1, -2) and Partner and Localizer of BRCA2 (PALB2) protein are tumour suppressors linked to a spectrum of malignancies, including breast cancer and Fanconi anemia. PALB2 coordinates functions of BRCA1 and BRCA2 during homology-directed repair (HDR) and interacts with several chromatin proteins. In addition to protein scaffold function, PALB2 binds DNA. The functional role of this interaction is poorly understood. We identified a major DNA-binding site of PALB2, mutations in which reduce RAD51 foci formation and the overall HDR efficiency in cells by 50%. PALB2 N-terminal DNA-binding domain (N-DBD) stimulates the function of RAD51 recombinase. Surprisingly, it possesses the strand exchange activity without RAD51. Moreover, N-DBD stimulates the inverse strand exchange and can use DNA and RNA substrates. Our data reveal a versatile DNA interaction property of PALB2 and demonstrate a critical role of PALB2 DNA binding for chromosome repair in cells.

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Novel RNA and DNA strand exchange activity of the PALB2 DNA binding domain and its critical role for DNA repair in cells

Résumé

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ASJC Scopus Subject Areas

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