RT Journal
A1 Liskovykh, Mikhail
A1 Goncharov, Nikolay V.
A1 Petrov, Nikolai
A1 Aksenova, Vasilisa
A1 Pegoraro, Gianluca
A1 Ozbun, Laurent L.
A1 Reinhold, William C.
A1 Varma, Sudhir
A1 Dasso, Mary
A1 Kumeiko, Vadim
A1 Masumoto, Hiroshi
A1 Earnshaw, William C.
A1 Larionov, Vladimir
A1 Kouprina, Natalay
T1 A novel assay to screen siRNA libraries identifies protein kinases required for chromosome transmission
JF Genome Research 
JO Genome Research 
YR 2019 
FD October 01 
VO 29 
IS 10 
SP 1719 
OP 1732 
DO 10.1101/gr.254276.119 
UL http://genome.cshlp.org/content/29/10/1719.abstract 
AB One of the hallmarks of cancer is chromosome instability (CIN), which leads to aneuploidy, translocations, and other chromosome aberrations. However, in the vast majority of human tumors the molecular basis of CIN remains unknown, partly because not all genes controlling chromosome transmission have yet been identified. To address this question, we developed an experimental high-throughput imaging (HTI) siRNA assay that allows the identification of novel CIN genes. Our method uses a human artificial chromosome (HAC) expressing the GFP transgene. When this assay was applied to screen an siRNA library of protein kinases, we identified PINK1, TRIO, IRAK1, PNCK, and TAOK1 as potential novel genes whose knockdown induces various mitotic abnormalities and results in chromosome loss. The HAC-based assay can be applied for screening different siRNA libraries (cell cycle regulation, DNA damage response, epigenetics, and transcription factors) to identify additional genes involved in CIN. Identification of the complete spectrum of CIN genes will reveal new insights into mechanisms of chromosome segregation and may expedite the development of novel therapeutic strategies to target the CIN phenotype in cancer cells.