Figure 5.

Schematic model demonstrating functional involvement of NPM1, RAD50 and XRCC5 in DSB-repair in the progression of ovarian cancer cells. Onset of environmental and therapeutic stress leads to the activation of ATM, which recruits MRN complex and phosphorylates H2AX histone variant. NPM1 and XRCC5 involved in HR and NHEJ pathways respectively. Knock-down of NPM1 and XRCC5 across alternatively activates NHEJ and HR pathways (red lines) towards maintaining DNA integrity and genomic stability. Under genomic stress conditions, knock-down of RAD50, NPM1 and XRCC5 DSB-repair proteins lead to the activation of p53/p21 signaling pathway resulted in onset of apoptosis of DSB-repair impaired cells. On other hand, cells surviving with impaired DSB-repair exhibit frequencies of reduced mitosis, mitotic irregularities and multi-polarity and aneuploidy, which conclusively facilitate genomic instability in transformed cells.