Unrepaired DNA damage facilitates elimination of uniparental chromosomes in interspecific hybrid cells

Zheng Wang, Hao Yin, Lei Lv, Yingying Feng, Shaopeng Chen, Junting Liang, Yun Huang, Xiaohua Jiang, Hanwei Jiang, Ihtisham Bukhari, Lijun Wu, Howard J Cooke, Qinghua Shi

Research output: Contribution to journalArticlepeer-review

Abstract

Elimination of uniparental chromosomes occurs frequently in interspecific hybrid cells. For example, human chromosomes are always eliminated during clone formation when human cells are fused with mouse cells. However, the underlying mechanisms are still elusive. Here, we show that the elimination of human chromosomes in human-mouse hybrid cells is accompanied by continued cell division at the presence of DNA damage on human chromosomes. Deficiency in DNA damage repair on human chromosomes occurs after cell fusion. Furthermore, increasing the level of DNA damage on human chromosomes by irradiation accelerates human chromosome loss in hybrid cells. Our results indicate that the elimination of human chromosomes in human-mouse hybrid cells results from unrepaired DNA damage on human chromosomes. We therefore provide a novel mechanism underlying chromosome instability which may facilitate the understanding of carcinogenesis.

Original languageEnglish
Pages (from-to)1345-56
Number of pages12
JournalCell Cycle
Volume13
Issue number8
DOIs
Publication statusPublished - 15 Apr 2014

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