Skip to main content
. 2020 May 23;21(10):3670. doi: 10.3390/ijms21103670

Figure 2.

Figure 2

Vitamin D may ameliorate defects in DNA repair associated with the loss of A-type lamins and increased activity of cathepsin (CTSL) L in triple-negative breast cancer (TNBC). A-type and other lamins play an important role in maintaining of cellular structure and genomic stability and their deficiency may occur in TNBC resulting in a series of effects, including CTSL activation, which leads to degradation of the TP53BP1 (tumor protein P53 binding protein 1) protein that is important in non-homologous end joining (NHEJ), the main DNA double-strand break repair (DSBR) system in humans. On the other hand, the loss of A-type lamins decreases the levels of DNA repair-associated breast cancer type 1 susceptibility (BRCA1) and RAD51 (RAD51 recombinase), major proteins of the other main DSBR system in humans—homologous recombination repair (HRR). Altogether, NHEJ and HRR deficiency contributes to genomic instability. Vitamin D may activate its receptor (VDR) and stimulate transcription of cystatin D that inhibits CTSL and in this way prevents TP53BP1 degradation, NHEJ deficiency and ameliorates genomic stability. Vitamin D may also prevent BRCA1 and RAD51 repression, but the exact mechanism underlying this effect is not completely known.