RAD52-dependent mitotic DNA synthesis is required for genome stability in Cyclin E1-overexpressing cells.

Audrey, Anastasia; Kok, Yannick P; Yu, Shibo; de Haan, Lauren; van de Kooij, Bert; van den Tempel, Nathalie; Chen, Mengting; de Boer, H Rudolf; van der Vegt, Bert; van Vugt, Marcel A T M

Audrey, Anastasia; Kok, Yannick P; Yu, Shibo; de Haan, Lauren; van de Kooij, Bert; van den Tempel, Nathalie; Chen, Mengting; de Boer, H Rudolf; van der Vegt, Bert; van Vugt, Marcel A T M.

Afiliación

Audrey A; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
Kok YP; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
Yu S; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
de Haan L; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
van de Kooij B; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
van den Tempel N; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
Chen M; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
de Boer HR; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
van der Vegt B; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
van Vugt MATM; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands. Electronic address: m.vugt@umcg.nl.

Cell Rep ; 43(4): 114116, 2024 Apr 23.

Article en En | MEDLINE | ID: mdl-38625790

ABSTRACT

ABSTRACT

Overexpression of Cyclin E1 perturbs DNA replication, resulting in DNA lesions and genomic instability. Consequently, Cyclin E1-overexpressing cancer cells increasingly rely on DNA repair, including RAD52-mediated break-induced replication during interphase. We show that not all DNA lesions induced by Cyclin E1 overexpression are resolved during interphase. While DNA lesions upon Cyclin E1 overexpression are induced in S phase, a significant fraction of these lesions is transmitted into mitosis. Cyclin E1 overexpression triggers mitotic DNA synthesis (MiDAS) in a RAD52-dependent fashion. Chemical or genetic inactivation of MiDAS enhances mitotic aberrations and persistent DNA damage. Mitosis-specific degradation of RAD52 prevents Cyclin E1-induced MiDAS and reduces the viability of Cyclin E1-overexpressing cells, underscoring the relevance of RAD52 during mitosis to maintain genomic integrity. Finally, analysis of breast cancer samples reveals a positive correlation between Cyclin E1 amplification and RAD52 expression. These findings demonstrate the importance of suppressing mitotic defects in Cyclin E1-overexpressing cells through RAD52.

Asunto(s)

Ciclina E; Inestabilidad Genómica; Mitosis; Proteínas Oncogénicas; Proteína Recombinante y Reparadora de ADN Rad52; Humanos; Ciclina E/metabolismo; Ciclina E/genética; Proteína Recombinante y Reparadora de ADN Rad52/metabolismo; Proteína Recombinante y Reparadora de ADN Rad52/genética; Proteínas Oncogénicas/metabolismo; Proteínas Oncogénicas/genética; Replicación del ADN; Línea Celular Tumoral; Daño del ADN; ADN/metabolismo; ADN/genética; Neoplasias de la Mama/genética; Neoplasias de la Mama/metabolismo; Neoplasias de la Mama/patología

Palabras clave

CCNE1; CP: Molecular biology; MiDAS; RAD52; break-induced replication; breast cancer; cell cycle; cyclin E1; mitosis; oncogene; replication stress

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Oncogénicas / Ciclina E / Inestabilidad Genómica / Proteína Recombinante y Reparadora de ADN Rad52 / Mitosis Límite: Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos

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