Aneuploidy refers to as a karyotype that some but not all chromosomes have an extra copy in addition to the 2-copy complement (2n). Aneuploidies often exhibit severe phenotypic defects. Aneuploidy is also a hallmark of tumor cells, which often exhibit karyotypic abnormalities involving multiple chromosomes (2n+x). However, it remains unclear how such complex karyotypes affect proliferation rate.
Researchers from QIAN Wenfeng Lab at the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences and Lucas B. Carey Lab at Peking University collaborated to tackle this problem. They generated about 100 2n+x yeast strains and found the proliferation defect was caused by the presence of protein complexes in which all subunits are at the 3-copy level.
Further collaboration with WANG Yingchun Lab at IGDB revealed that an increase in DNA copy number increases the dosage of proteins in a protein complex only if the copy number of all subunits increases.
It is because the successful assembly of them helps to escape from the protein surveillance system that specifically degrades unassembled subunits. The overdosage of a protein complex, in turn, affects proliferation by disrupting the stoichiometric balance among the components of a signaling pathway.
The further analyses of The Cancer Genome Atlas and the Mitelman database revealed that what found in yeast cells also applied to human cancer cells.
Collectively, this study provides a new explanation for the proliferation defect in aneuploid cells and extends our understanding of tumorigenesis.
The work was supported by the National Natural Science Foundation of China.
Figure Overdosage of balanced protein complexes reduces the proliferation rate in the complex aneuploid cells (Image by IGDB)
