Moreover, fumarate accumulation facilitates G2-M transition and causes a decrease in the G2 checkpoint, which tends to damage the DNA and confers resistance to ionizing radiation in FH-deficient cells, indicating that FH loss and fumarate accumulation can give rise to genomic instability that can trigger HLRCC formation (58). This evidence concerns the gene FH and hereditary leiomyomatosis and renal cell cancer.