POLB

POLB is the gene that encodes DNA polymerase beta (Pol β), a DNA repair enzyme in eukaryotes. Pol β is a member of the X-family polymerases and plays a central role in base excision repair, filling single-nucleotide gaps that arise after removal of damaged bases, and providing deoxyribose phosphate lyase activity that removes the sugar-phosphate remnant.

The protein is approximately 39 kDa and consists of two domains: an N-terminal 8 kDa lyase domain and a C-terminal 31 kDa polymerase domain. The polymerase domain carries the catalytic motifs required for DNA synthesis, while the lyase domain removes the abasic sugar-phosphate group. The enzyme typically operates in a multi-protein BER complex with XRCC1, DNA ligase III, PARP1, and other factors, in collaboration with PCNA.

Pol β localizes mainly to the nucleus, where most BER occurs, and is expressed broadly across tissues; some studies report mitochondrial BER involvement under certain conditions.

Regulation includes post-translational modifications and protein–protein interactions that modulate activity and stability; the enzyme's fidelity is moderate and specialized for short-patch BER rather than processive replication.

Clinical significance: POLB mutations and polymorphisms have been studied for cancer risk; altered expression has been observed in various tumors; both deficiency and overexpression can affect cellular sensitivity to DNA-damaging agents.

Evolution: Pol β is conserved in vertebrates; multiple transcripts and splice variants have been described; the gene is part of the DNA polymerase X family.