Induction of apoptotic endonuclease EndoG with DNA-damaging agents initiates alternative splicing of telomerase catalytic subunit hTERT and inhibition of telomerase activity hTERT in human CD4+ and CD8+ T-lymphocytes

Zhdanov D.D.1 , Vasina D.A.2, Orlova V.S.2, Orlova E.V.3, Grishin D.V.1, Gladilina Yu.A.1, Pokrovskaya M.V.1, Aleksandrova S.S.1, Sokolov N.N.1

1. Institute of Biomedical Chemistry, Moscow, Russia
2. Peoples Friendship University of Russia, Moscow, Russia
3. Institute of Theoretical and Experimental Biophysics, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20176304296      PubMed Id: 28862599
Year: 2017  Volume: 63  Issue: 4  Pages: 296-305
Activity of telomerase catalytic subunit hTERT (human Telomerase Reverse Transcriptase) can be regulated by alternative splicing of its mRNA. At present time exact mechanism of hTERT splicing is not fully understood. Apoptotic endonuclease EndoG is known to participate this process. EndoG expression is induced by DNA damages. The aim of this work was to investigate the ability of DNA-damaging agents with different mechanism of action to induce EndoG expression and inhibit telomerase activity due to the activation of hTERT alternative splicing in normal activated human CD4+ and CD8+ T-lymphocytes. All investigated DNA-damaging agents were able to induce EndoG expression. Cisplatin, a therapeutic compound, producing DNA cross-links induced the highest level of DNA damages and EndoG expression. Incubation of CD4+ and CD8+ T-cells with cisplatin caused the changes in proportion of hTERT splice variants and inhibition of telomerase activity.
Download PDF:

Zhdanov D.D., Vasina D.A., Orlova V.S., Orlova E.V., Grishin D.V., Gladilina Yu.A., Pokrovskaya M.V., Aleksandrova S.S., Sokolov N.N. (2017) Biomeditsinskaya khimiya, 63(4), 296-305.
This paper is also available as the English translation:10.1134/S1990750818020154
 2019 (vol 65)
 2018 (vol 64)
 2017 (vol 63)
 2016 (vol 62)
 2015 (vol 61)
 2014 (vol 60)
 2013 (vol 59)
 2012 (vol 58)
 2011 (vol 57)
 2010 (vol 56)
 2009 (vol 55)
 2008 (vol 54)
 2007 (vol 53)
 2006 (vol 52)
 2005 (vol 51)
 2004 (vol 50)
 2003 (vol 49)

© Institute of Biomedical Chemistry, Moscow, Russia