title: Unrepaired DNA damage facilitates elimination of uniparental chromosomes in interspecific hybrid cells.
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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Hefei Institutes of Physical Science, Chinese Academy of Sciences; Hefei, China.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Hefei Institutes of Physical Science, Chinese Academy of Sciences; Hefei, China.
authors.forename: Junting
authors.initials: J
authors.lastname: Liang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China.
authors.forename: Hanwei
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China.
authors.forename: Ihtisham
authors.initials: I
authors.lastname: Bukhari
authors.affiliation: Hefei Institutes of Physical Science, Chinese Academy of Sciences; Hefei, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China; MRC Human Genetics Unit and Institute of Genetics and Molecular Medicine; University of Edinburgh; Western General Hospital; Edinburgh, UK.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Cooke
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China; Hefei Institutes of Physical Science, Chinese Academy of Sciences; Hefei, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000818:Animals; D002459:Cell Fusion; D049109:Cell Proliferation; D043171:Chromosomal Instability; D002877:Chromosomes, Human; D004249:DNA Damage; D004260:DNA Repair; D045325:HCT116 Cells; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology*; D051379:Mice; D008938:Mitosis / Q000235:genetics; D041681:NIH 3T3 Cells
keywords: DNA damage repair; cell cycle regulation; chromosomal elimination; chromosome instability; hybrid cells