Short-term molecular consequences of chromosome mis-segregation for genome stability.

Autor: Garribba L; Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., De Feudis G; Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Martis V; Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Galli M; IFOM ETS - The AIRC Institute of Molecular Oncology, via Adamello 16, 20139, Milan, Italy., Dumont M; Institut Curie, PSL Research University, CNRS, UMR144, Paris, France., Eliezer Y; Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Wardenaar R; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, the Netherlands., Ippolito MR; Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Iyer DR; Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA, 01605, USA., Tijhuis AE; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, the Netherlands., Spierings DCJ; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, the Netherlands., Schubert M; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, the Netherlands., Taglietti S; Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Soriani C; Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Gemble S; Institut Curie, PSL Research University, CNRS, UMR144, Paris, France., Basto R; Institut Curie, PSL Research University, CNRS, UMR144, Paris, France., Rhind N; Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA, 01605, USA., Foijer F; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, the Netherlands., Ben-David U; Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Fachinetti D; Institut Curie, PSL Research University, CNRS, UMR144, Paris, France., Doksani Y; IFOM ETS - The AIRC Institute of Molecular Oncology, via Adamello 16, 20139, Milan, Italy., Santaguida S; Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy. stefano.santaguida@ieo.it.; Department of Oncology and Hemato-Oncology, University of Milan, Via Santa Sofia 9/1, 20122, Milan, Italy. stefano.santaguida@ieo.it.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Mar 11; Vol. 14 (1), pp. 1353. Date of Electronic Publication: 2023 Mar 11.
DOI: 10.1038/s41467-023-37095-7
Abstrakt: Chromosome instability (CIN) is the most common form of genome instability and is a hallmark of cancer. CIN invariably leads to aneuploidy, a state of karyotype imbalance. Here, we show that aneuploidy can also trigger CIN. We found that aneuploid cells experience DNA replication stress in their first S-phase and precipitate in a state of continuous CIN. This generates a repertoire of genetically diverse cells with structural chromosomal abnormalities that can either continue proliferating or stop dividing. Cycling aneuploid cells display lower karyotype complexity compared to the arrested ones and increased expression of DNA repair signatures. Interestingly, the same signatures are upregulated in highly-proliferative cancer cells, which might enable them to proliferate despite the disadvantage conferred by aneuploidy-induced CIN. Altogether, our study reveals the short-term origins of CIN following aneuploidy and indicates the aneuploid state of cancer cells as a point mutation-independent source of genome instability, providing an explanation for aneuploidy occurrence in tumors.
(© 2023. The Author(s).)
Databáze: MEDLINE
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