H2AX phosphorylation, its role in DNA damage response and cancer therapy

Monika Podhorecka; Andrzej Składanowski; Przemysław Bożko

H2AX phosphorylation, its role in DNA damage response and cancer therapy

Abstract

Double-strand breaks (DSBs) are the most deleterious DNA lesions, which, if left unrepaired, may have severe consequences for cell survival, as they lead to chromosome aberrations, genomic instability, or cell death. Various physical, chemical, and biological factors are involved in DSB induction. Cells respond to DNA damage by activating the so-called DNA damage response (DDR), a complex molecular mechanism developed to detect and repair DNA damage. The formation of DSBs triggers activation of many factors, including phosphorylation of the histone variant H2AX, producing gammaH2AX. Phosphorylation of H2AX plays a key role in DDR and is required for the assembly of DNA repair proteins at the sites containing damaged chromatin as well as for activation of checkpoints proteins which arrest the cell cycle progression. In general, analysis of gammaH2AX expression can be used to detect the genotoxic effect of different toxic substances. When applied to clinical samples from cancer patients, evaluation of gammaH2AX levels may allow not only to monitor the efficiency of anticancer treatment but also to predict of tumor cell sensitivity to DNA damaging anticancer agents and toxicity of anticancer treatment toward normal cells.

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Category:: Articles
Type:: artykuły w czasopismach recenzowanych i innych wydawnictwach ciągłych
Published in:: Journal of Nucleic Acids no. 2010, pages 1 - 9,
ISSN: 2090-0201
Language:: English
Publication year:: 2010
Bibliographic description:: Podhorecka M., Składanowski A., Bożko P.: H2AX phosphorylation, its role in DNA damage response and cancer therapy// Journal of Nucleic Acids. -Vol. 2010., (2010), s.1-9
Verified by:: Gdańsk University of Technology