Novel screen for anti-cancer drugs that elevate chromosome instability (CIN) using human artificial chromosome (HAC)
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Natalay Kouprina1, Yves Pommier1 and Vladimir Larionov1
1Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Natalay Kouprina, email: [email protected]
Yves Pommier, email: [email protected]
Vladimir Larionov, email: [email protected]
Keywords: chromosome instability; CIN; human artificial chromosome; HAC; anti-cancer drugs
Received: November 07, 2018 Accepted: November 16, 2018 Published: December 07, 2018
Human artificial chromosomes (HACs) bearing functional kinetochores have been exploited as promising systems for gene delivery and expression and in studies of different epigenetic modifications on kinetochore structure and function. The HAC-based technology has been also used to develop drug screening and assessment strategies to manipulate the CIN (chromosome instability) phenotype in cancer cells. More recently, we designed a new protocol for systematic analysis of compounds specifically targeting telomeres and telomerase. This approach used two isogenic cell lines containing a circular HAC (lacking telomeres) and a linear HAC (containing telomeres): compounds that target telomerase or telomeres should preferentially induce loss of the linear HAC but not the circular HAC. This platform enables identification and ranking of compounds that greatly increase chromosome mis-segregation rates as a result of telomere dysfunction and may expedite the development of new therapeutic strategies for cancer treatment.
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