Physiological concentrations of glucocorticoids induce pathological DNA double‐strand breaks

Autor: Salma Akter, Akihiro Shimba, Koichi Ikuta, Md. Rasel Al Mahmud, Shintaro Yamada, Hiroyuki Sasanuma, Masataka Tsuda, Masakatsu Sone, Yukio Ago, Kenichi Murai, Hisashi Tanaka, Shunichi Takeda
Rok vydání: 2022
Předmět:
Zdroj: Genes to Cells. 28:53-67
ISSN: 1365-2443
1356-9597
Popis: Steroid hormones induce the transcription of target genes by activating nuclear receptors. Early transcriptional response to various stimuli, including hormones, involves the active catalysis of topoisomerase II (TOP2) at transcription regulatory sequences. TOP2 untangles DNAs by transiently generating double-strand breaks (DSBs), where TOP2 covalently binds to DSB ends. When TOP2 fails to rejoin, called "abortive" catalysis, the resulting DSBs are repaired by tyrosyl-DNA phosphodiesterase 2 (TDP2) and non-homologous end-joining (NHEJ). A steroid, cortisol, is the most important glucocorticoid, and dexamethasone (Dex), a synthetic glucocorticoid, is widely used for suppressing inflammation in clinics. We here revealed that clinically relevant concentrations of Dex and physiological concentrations of cortisol efficiently induce DSBs in G
Databáze: OpenAIRE
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