Products Cited in Publications Worldwide Polyploidy mitigates the impact of DNA damage while simultaneously bearing its burden

Polyploidy mitigates the impact of DNA damage while simultaneously bearing its burden

Hayashi, Kazuki; Horisaka, Kisara; Harada, Yoshiyuki; Ogawa, Yuta; Yamashita, Takako; Kitano, Taku; Wakita, Masahiro; Fukusumi, Takahito; Inohara, Hidenori; Hara, Eiji; Matsumoto, Tomonori

DOI: PMID:

Abstract

Polyploidy is frequently enhanced under pathological conditions, such as tissue injury and cancer in humans. Polyploidization is critically involved in cancer evolution, including cancer initiation and the acquisition of drug resistance. However, the effect of polyploidy on cell fate remains unclear. In this study, we explored the effects of polyploidization on cellular responses to and progression. Through various comparisons based on ploidy stratifications of cultured cells, we found that polyploidization and the accumulation of genomic mutually induce each other, resulting in polyploid cells consistently containing more genomic than diploid cells under both physiological and stress conditions. Notably, despite substantial , polyploid cells demonstrated a higher tolerance to its impact, exhibiting delayed arrest and reduced secretion of inflammatory cytokines associated with DNA damage-induced senescence. Consistently, in mice with ploidy tracing, hepatocytes with high ploidy appeared to potentially persist in the damaged liver, while being susceptible to . Polyploidy acts as a reservoir of genomic damage by mitigating the impact of , while simultaneously enhancing its accumulation.

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