Research Paper Volume 9, Issue 9 pp 1957—1970

The G-quadruplex DNA stabilizing drug pyridostatin promotes DNA damage and downregulates transcription of Brca1 in neurons

Figure 7. A model of the Brca1 gene downregulation by pyridostatin. (A) Transcription of the Brca1 gene in primary neurons under basal conditions. (B) Pyridostatin binds to and stabilizes the G-quadruplex structures present in the Brca1 gene promoter sequence. The pyridostatin/DNA complex stalls DNA polymerase during transcription and downregulates Brca1 gene expression. (1) Brca1 downregulation may then hinder DNA damage repair and DNA DSBs accumulate as a result. (2) In addition, DNA damage may occur due the action of endonucleases through a mechanism of transcription–coupled–repair poisoning [25].