PARP1 GENE KNOCKOUT SUPPRESSES EXPRESSION OF DNA BASE EXCISION REPAIR GENES

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Abstract

The effect of PARP1 knockout in HEK293 cells on the gene expression of DNA base excision repair (BER) proteins was studied. It was shown that the expression of all differentially expressed genes (DEGs) of BER was reduced by knockout. The expression of the DNA glycosylase gene NEIL1, which is considered to be one of the common “hubs” for binding BER proteins, has changed the most. The expression of genes of auxiliary subunits of DNA polymerases δ and ε is also significantly reduced. The PARP1 gene knockout cell line obtained is an adequate cell model for studying the activity of the BER process in the absence of PARP1 and testing drugs aimed at inhibiting repair processes. It has been found for the first time that knockout of the PARP1 gene results in a significant change in the level of expression of proteins responsible for ribosome biogenesis and the functioning of the proteasome.

About the authors

A. L. Zakharenko

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: dyrkheeva.n.s@gmail.com
Russian Federation, Novosibirsk

A. A. Malakhova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; Federal Research Centre Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; E.N. Meshalkin National medical research center of the Ministry of Health of the Russian Federation

Email: dyrkheeva.n.s@gmail.com
Russian Federation, Novosibirsk; Russian Federation, Novosibirsk; Russian Federation, Novosibirsk

N. S. Dyrkheeva

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: dyrkheeva.n.s@gmail.com
Russian Federation, Novosibirsk

L. S. Okorokova

AcademGene LLC

Email: dyrkheeva.n.s@gmail.com
Russian Federation, Novosibirsk

S. P. Medvedev

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; Federal Research Centre Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; E.N. Meshalkin National medical research center of the Ministry of Health of the Russian Federation

Email: dyrkheeva.n.s@gmail.com
Russian Federation, Novosibirsk; Russian Federation, Novosibirsk; Russian Federation, Novosibirsk

S. M. Zakian

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; Federal Research Centre Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; E.N. Meshalkin National medical research center of the Ministry of Health of the Russian Federation

Email: dyrkheeva.n.s@gmail.com
Russian Federation, Novosibirsk; Russian Federation, Novosibirsk; Russian Federation, Novosibirsk

M. R. Kabilov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: dyrkheeva.n.s@gmail.com
Russian Federation, Novosibirsk

A. A. Tupikin

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: dyrkheeva.n.s@gmail.com
Russian Federation, Novosibirsk

O. I. Lavrik

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: lavrik@niboch.nsc.ru
Russian Federation, Novosibirsk

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