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. 2020 Jul 22;12:6123–6135. doi: 10.2147/CMAR.S221001

Figure 1.

Figure 1

Overview of the HR pathway in PTEN-deficient EC cells. When DSBs occur, ATM, ATR and CHK1/2 kinases phosphorylate BRCA1, that is stabilized by BARD1. BRCA2, whose correct conformation is maintained by DSS1 and PALB2, carries RAD51 to the site of DNA damage, where it forms nucleoprotein filaments and stabilizes DNA double strands. The EGFR activates PI3K/AKT pathway, that in turn inhibits p53. Conversely, PTEN inhibits the PI3K pathway and thus activates p53, that induces cell apoptosis and cycle arrest and increases the expression of the RAD51 and the MRN complex (RAD50, MRE11, NBS1), involved in the DSBs repair. Moreover, PTEN upregulates RAD51. Therefore, mutant PTEN inhibits p53 and RAD51 expression, thus impairing the HR system. Similarly, mutant p53 downregulates the MRN complex and RAD51 levels.