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

Autor:	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.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Apr 23; Vol. 43 (4), pp. 114116. Date of Electronic Publication: 2024 Apr 15.
DOI:	10.1016/j.celrep.2024.114116
Abstrakt:	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. Competing Interests: Declaration of interests B.v.d.V. reports honoraria received by UMCG for expertise or scientific advisory board/consultancy (on request): Visiopharm, Philips, MSD/Merck, and Daiichi-Sankyo/AstraZeneca, as well as speaker’s fees from Visiopharm, Diaceutics, and MSD/Merck. M.A.T.M.v.V. has acted on the scientific advisory boards of Nodus Oncology and RepareTx, unrelated to this work. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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