DNA polymerase eta (POLH)

DNA polymerase eta (POLH) is a specialized member of the Y-family DNA polymerases involved in translesion synthesis, allowing replication to proceed past DNA lesions such as thymine dimers created by UV light. Unlike most polymerases that stall at damaged DNA, POLH efficiently and accurately bypasses these lesions, protecting cells from apoptosis due to replication blockage. Mutations in POLH cause xeroderma pigmentosum variant (XP-V), an autosomal recessive disorder characterized by heightened sensitivity to sunlight and increased frequency of skin cancer. Structurally, POLH features a spacious active site enabling lesion bypass, and interacts with the replication protein PCNA. Its error-prone nature confers a risk for mutagenesis when repair is not tightly regulated.

Other names

POLHRAD30RAD30AXPVXP-VRAD30 homolog AXeroderma pigmentosum variant type proteinpolymerase (DNA directed), etapolymerase (DNA) eta

Agents that inhibit POLH (potentially hypothetical) would block translesion DNA synthesis, increasing sensitivity to DNA-damaging agents. No established drugs/mechanisms specifically for this enzyme.