Abstract
The G2/M checkpoint is activated on DNA damage by the ATM and ATR kinases that are regulated by post-translational modifications. In this paper, the transcriptional co-regulation of ATM and ATR by SMARCAL1 and BRG1, both members of the ATP-dependent chromatin remodeling protein family, is described. SMARCAL1 and BRG1 co-localize on the promoters of ATM and ATR; downregulation of SMARCAL1 and BRG1 results in transcriptional repression of ATM/ATR and overriding of the G2/M checkpoint leading to mitotic abnormalities. On doxorubicin-induced DNA damage, SMARCAL1 and BRG1 are upregulated and these two proteins in turn, upregulate the expression of ATM/ATR. The transcriptional response to DNA damage is feedback regulated by phospho-ATM as it binds to the promoters of SMARCAL1, BRG1, ATM and ATR on DNA damage. The regulation of ATM/ATR is rendered non-functional in Schimke Immuno-Osseous Dysplasia where SMARCAL1 is mutated and in Coffin-Siris Syndrome where BRG1 is mutated. Thus, an intricate transcriptional regulation of DNA damage response genes mediated by SMARCAL1 and BRG1 is present in mammalian cells.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
