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siREV3L is a small interfering RNA (siRNA) designed to silence the expression of the *REV3L* gene, which encodes the catalytic subunit of DNA polymerase zeta (Pol ζ). Pol ζ is a specialized B-family DNA polymerase that plays a critical role in translesion synthesis (TLS), a DNA damage tolerance mechanism that allows cells to replicate past bulky DNA lesions, such as those induced by ultraviolet light or platinum-based chemotherapeutics. By depleting REV3L, siREV3L inhibits the TLS pathway, thereby increasing the accumulation of DNA double-strand breaks and sensitizing cancer cells to DNA-damaging treatments. This approach is primarily investigated in preclinical research as a combination therapy to overcome chemoresistance in various malignancies, including prostate, breast, cervical, and ovarian cancers.
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