DNA polymerase beta

POLB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BPX, 1BPY, 1BPZ, 1MQ2, 1MQ3, 1TV9, 1TVA, 1ZJM, 1ZJN, 1ZQA, 1ZQB, 1ZQC, 1ZQD, 1ZQE, 1ZQF, 1ZQG, 1ZQH, 1ZQI, 1ZQJ, 1ZQK, 1ZQL, 1ZQM, 1ZQN, 1ZQO, 1ZQP, 1ZQQ, 1ZQR, 1ZQS, 1ZQT, 2FMP, 2FMQ, 2FMS, 2I9G, 2ISO, 2ISP, 2P66, 2PXI, 3C2K, 3C2L, 3C2M, 3GDX, 3ISB, 3ISC, 3ISD, 3JPN, 3JPO, 3JPP, 3JPQ, 3JPR, 3JPS, 3JPT, 3LK9, 3MBY, 3OGU, 3RH4, 3RH5, 3RH6, 3RJE, 3RJF, 3RJG, 3RJH, 3RJI, 3RJJ, 3RJK, 3TFR, 3TFS, 4DO9, 4DOA, 4DOB, 4DOC, 4F5N, 4F5O, 4F5P, 4F5Q, 4F5R, 4GXI, 4GXJ, 4GXK, 4JWM, 4JWN, 4KLD, 4KLE, 4KLF, 4KLG, 4KLH, 4KLI, 4KLJ, 4KLL, 4KLM, 4KLO, 4KLQ, 4KLS, 4KLT, 4KLU, 4LVS, 4M2Y, 4M47, 4M9G, 4M9H, 4M9J, 4M9L, 4M9N, 4MF2, 4MF8, 4MFA, 4MFC, 4MFF, 4NLK, 4NLN, 4NLZ, 4NM1, 4NM2, 4NXZ, 4NY8, 4O5C, 4O5E, 4O5K, 4O9M, 4P2H, 4PGQ, 4PGX, 4PGY, 4PH5, 4PHA, 4PHD, 4PHE, 4PHP, 4PPX, 4R63, 4R64, 4R65, 4R66, 4RPX, 4RPY, 4RPZ, 4RQ0, 4RQ1, 4RQ2, 4RQ3, 4RQ4, 4RQ5, 4RQ6, 4RQ7, 4RQ8, 4RT2, 4RT3, 4TUP, 4TUQ, 4TUR, 4TUS, 4UAW, 4UAY, 4UAZ, 4UB1, 4UB2, 4UB3, 4UB4, 4UB5, 4UBB, 4UBC, 7ICE, 7ICF, 7ICG, 7ICH, 7ICI, 7ICJ, 7ICK, 7ICL, 7ICM, 7ICN, 7ICO, 7ICP, 7ICQ, 7ICR, 7ICS, 7ICT, 7ICU, 7ICV, 8ICA, 8ICB, 8ICC, 8ICE, 8ICF, 8ICG, 8ICH, 8ICI, 8ICJ, 8ICK, 8ICL, 8ICM, 8ICN, 8ICO, 8ICP, 8ICQ, 8ICR, 8ICS, 8ICT, 8ICU, 8ICV, 8ICW, 8ICX, 8ICY, 8ICZ, 9ICA, 9ICB, 9ICC, 9ICE, 9ICF, 9ICG, 9ICH, 9ICI, 9ICJ, 9ICK, 9ICL, 9ICM, 9ICN, 9ICO, 9ICP, 9ICQ, 9ICR, 9ICS, 9ICT, 9ICU, 9ICV, 9ICW, 9ICX, 9ICY, 5BOL, 5BOM, 5BPC, 5DB8, 5DBB, 5DBA, 5DB7, 5DBC, 5DB9, 5DB6, 4YMN, 4YN4, 4YMO, 4YMM, 4Z6C, 4Z6F, 4Z6D, 4Z6E
Identifiers
Aliases	POLB, DNA polymerase beta
External IDs	OMIM: 174760; MGI: 97740; HomoloGene: 2013; GeneCards: POLB; OMA:POLB - orthologs
Gene location (Mouse) Chr. Chromosome 8 (mouse)[1] Band 8 A2|8 11.42 cM Start 23,118,142 bp[1] End 23,143,451 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte cerebellar hemisphere secondary oocyte sperm cerebellar vermis ganglionic eminence thoracic diaphragm parotid gland monocyte pons Top expressed in spermatid spermatocyte seminiferous tubule intercostal muscle hair follicle facial motor nucleus fossa esophagus sternocleidomastoid muscle condyle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity DNA binding nucleotidyltransferase activity microtubule binding metal ion binding damaged DNA binding protein binding lyase activity enzyme binding DNA-directed DNA polymerase activity DNA-(apurinic or apyrimidinic site) endonuclease activity DNA polymerase DNA polymerase activity Cellular component cytoplasm nucleoplasm spindle microtubule microtubule nucleus protein-containing complex Biological process neuron apoptotic process somatic hypermutation of immunoglobulin genes pyrimidine dimer repair nucleotide-excision repair, DNA gap filling DNA-dependent DNA replication DNA biosynthetic process homeostasis of number of cells response to hyperoxia human ageing spleen development salivary gland morphogenesis cellular response to DNA damage stimulus immunoglobulin heavy chain V-D-J recombination DNA replication somatic diversification of immunoglobulins base-excision repair, gap-filling intrinsic apoptotic signaling pathway in response to DNA damage response to ethanol inflammatory response lymph node development response to gamma radiation DNA repair apoptotic process base-excision repair base-excision repair, DNA ligation protein deubiquitination double-strand break repair via nonhomologous end joining Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5423 18970 Ensembl ENSG00000070501 ENSMUSG00000031536 UniProt P06746 Q8K409 RefSeq (mRNA) NM_002690 NM_011130 RefSeq (protein) NP_002681 NP_035260 Location (UCSC) n/a Chr 8: 23.12 – 23.14 Mb PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Stem loopII regulatory element in POLB
Predicted secondary structure of the stem loopII (M2) regulatory element in POLB
Identifiers
Symbol	POLB
Rfam	RF01455
NCBI Gene	5423
HGNC	9174
OMIM	174760
RefSeq	NM_002690
Other data
RNA type	Cis-reg
Domain(s)	Mammalia
Locus	Chr. 8 p11.2
PDB structures	PDBe

DNA polymerase beta, also known as POLB, is an enzyme present in eukaryotes. In humans, it is encoded by the POLB gene.^[4]

Function

In eukaryotic cells, DNA polymerase beta (POLB) performs base excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance.^[4]

The mitochondrial DNA of mammalian cells is constantly under attack from oxygen radicals released during ATP production. Mammalian cell mitochondria contain an efficient base excision repair system employing POLB that removes some frequent oxidative DNA damages.^[5] POLB thus has a key role in maintaining the stability of the mitochondrial genome.^[5]

An analysis of the fidelity of DNA replication by polymerase beta in the neurons from young and very aged mice indicated that aging has no significant effect on the fidelity of DNA synthesis by polymerase beta.^[6] This finding was considered to provide evidence against the error catastrophe theory of aging.^[6][7]

Base excision repair

Cabelof et al. measured the ability to repair DNA damage by the BER pathway in tissues of young (4-month-old) and old (24-month-old) mice.^[8] In all tissues examined (brain, liver, spleen and testes) the ability to repair DNA damage declined significantly with age, and the reduction in repair capability correlated with decreased levels of DNA polymerase beta at both the protein and messenger RNA levels. Numerous investigators have reported an accumulation of DNA damage with age, especially in brain and liver.^[9] Cabelof et al.^[8] suggested that the inability of the BER pathway to repair damages over time may provide a mechanistic explanation for the frequent observations of DNA accumulation of damage with age.

Regulation of expression

DNA polymerase beta maintains genome integrity by participating in base excision repair. Overexpression of POLB mRNA has been correlated with a number of cancer types, whereas deficiencies in POLB results in hypersensitivity to alkylating agents, induced apoptosis, and chromosomal breaking. Therefore, it is essential that POLB expression is tightly regulated.^{[10][11][12][13]}

POLB gene is upregulated by CREB1 transcription factor's binding to the cAMP response element (CRE) present in the promoter of the POLB gene in response to exposure to alkylating agents.^[14][15] POLB gene expression is also regulated at the post transcriptional level as the 3'UTR of the POLB mRNA has been shown to contain three stem-loop structures that influence gene expression.^[16] These three-stem loop structures are known as M1, M2, and M3, where M2 and M3 have a key role in gene regulation. M3 contributes to gene expression, as it contains the polyadenylation signal followed by the cleavage and polyadenylation site, thereby contributing to pre-mRNA processing. M2 has been shown to be evolutionary conserved, and, through mutagenesis, it was shown that this stem loop structure acts as a RNA destabilizing element.

In addition to these cis-regulatory elements present within the 3'UTR a trans-acting protein, HAX1 is thought to contribute to the regulation of gene expression. Yeast three-hybrid assays have shown that this protein binds to the stem loops within the 3'UTR of the POLB mRNA, however the exact mechanism in how this protein regulates gene expression is still to be determined.

Interactions

DNA polymerase beta has been shown to interact with PNKP^[17] and XRCC1.^{[18][19][20][21]}

See also

• POLA1
• POLA2

References

Further reading

External links

• Rfam entry for the stem loopII (M2) regulatory element in POLB