DNA polymerases involved in repair

DNA polymerases involved in repair are a specialized group of enzymes responsible for maintaining genomic integrity by filling gaps and bypassing lesions during various DNA repair pathways [14, 15]. Unlike high-fidelity replicative polymerases such as DNA polymerase delta and epsilon, these repair polymerases—including members of the X-family (Pol Beta, Lambda, Mu) and Y-family (Pol Eta, Iota, Kappa)—often lack proofreading activity and can synthesize DNA across damaged templates, a process known as translesion synthesis [1, 3, 15]. In the context of oncology, these enzymes are critical therapeutic targets because they contribute to chemoresistance by repairing damage caused by platinum agents or ionizing radiation [1, 17, 20]. For instance, DNA polymerase theta (Pol Theta) has emerged as a prominent synthetic lethal target in homologous recombination-deficient cancers, such as those with BRCA1 or BRCA2 mutations, as it provides an alternative, error-prone repair pathway that these cells depend upon for survival [4, 9, 13]. Inhibiting these polymerases can sensitize tumor cells to conventional therapies or selectively induce cell death in specific genetic backgrounds, offering a strategy for precision medicine [8, 10, 16]. Furthermore, deficiencies in these enzymes are linked to hereditary conditions like xeroderma pigmentosum, highlighting their essential role in protecting against environmental genotoxins [3, 8].

Other names

DNA repair polymerasesSpecialized DNA polymerasesTranslesion synthesis polymerasesFamily X polymerasesFamily Y polymerasesDNA-directed DNA polymerases (repair-associated)

Inhibition of DNA synthesis during repair, synthetic lethality in homologous recombination-deficient cells, and sensitization to DNA-damaging agents through the prevention of lesion bypass or gap filling.