POLD3 and colorectal carcinoma: Activation of ALT in MSI s-CRC is mainly due to overexpression of RAD51 (HR Step 1), POLD3, and RFC1 (polymerase δ subunit, HR Step 2) which suggests activation of template directed synthesis of telomeres via the RFC1-PCNA-POLD3 axis (41) (Figure 6).