DNA polymerase beta

Polymerase (DNA directed), beta

PDB rendering based on 1bno.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPOLB ; MGC125976
External IDsOMIM: 174760 MGI: 97740 HomoloGene: 2013 ChEMBL: 2392 GeneCards: POLB Gene
EC number2.7.7.7
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez542318970
EnsemblENSG00000070501ENSMUSG00000031536
UniProtP06746Q8K409
RefSeq (mRNA)NM_002690NM_011130
RefSeq (protein)NP_002681NP_035260
Location (UCSC)Chr 8:
42.2 – 42.23 Mb		Chr 8:
22.63 – 22.65 Mb
PubMed search
Stem loopII regulatory element in POLB
Predicted secondary structure of the stem loopII (M2) regulatory element in POLB
Identifiers
Symbol POLB
Rfam RF01455
Entrez 5423
HUGO POLB
OMIM 174760
RefSeq NM_002690
Other data
RNA type Cis-reg
Domain(s) Mammalia
Locus Chr. 8 p11.2

Polymerase (DNA directed), beta, also known as POLB, is an enzyme that, in humans, is encoded by the POLB gene.[1]

Function

In eukaryotic cells, DNA polymerase beta (POLB) performs base excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance.[1]

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 [ref7]. Therefore, it is essential that POLB expression is tightly regulated.[2][3][4][5]

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.[6][7] 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.[8] 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[9] and XRCC1.[10][11][12][13]

See also

References

  1. ↑ 1.0 1.1 "Entrez Gene: POLB polymerase (DNA directed), beta".
  2. ↑ Canitrot Y; Cazaux C; Fréchet M et al. (October 1998). "Overexpression of DNA polymerase beta in cell results in a mutator phenotype and a decreased sensitivity to anticancer drugs". Proc. Natl. Acad. Sci. U.S.A. 95 (21): 12586–90. doi:10.1073/pnas.95.21.12586. PMC 22874. PMID 9770529.
  3. ↑ Bergoglio V; Pillaire MJ; Lacroix-Triki M et al. (June 2002). "Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis". Cancer Res. 62 (12): 3511–4. PMID 12067997.
  4. ↑ Bergoglio V; Canitrot Y; Hogarth L et al. (September 2001). "Enhanced expression and activity of DNA polymerase beta in human ovarian tumor cells: impact on sensitivity towards antitumor agents". Oncogene 20 (43): 6181–7. doi:10.1038/sj.onc.1204743. PMID 11593426.
  5. ↑ Srivastava DK, Husain I, Arteaga CL, Wilson SH (June 1999). "DNA polymerase beta expression differences in selected human tumors and cell lines". Carcinogenesis 20 (6): 1049–54. doi:10.1093/carcin/20.6.1049. PMID 10357787.
  6. ↑ He F, Yang XP, Srivastava DK, Wilson SH (January 2003). "DNA polymerase beta gene expression: the promoter activator CREB-1 is upregulated in Chinese hamster ovary cells by DNA alkylating agent-induced stress". Biol. Chem. 384 (1): 19–23. doi:10.1515/BC.2003.003. PMID 12674496.
  7. ↑ Narayan S, He F, Wilson SH (August 1996). "Activation of the human DNA polymerase beta promoter by a DNA-alkylating agent through induced phosphorylation of cAMP response element-binding protein-1". J. Biol. Chem. 271 (31): 18508–13. doi:10.1074/jbc.271.31.18508. PMID 8702497.
  8. ↑ Sarnowska E; Grzybowska EA; Sobczak K et al. (2007). "Hairpin structure within the 3'UTR of DNA polymerase beta mRNA acts as a post-transcriptional regulatory element and interacts with Hax-1". Nucleic Acids Res. 35 (16): 5499–510. doi:10.1093/nar/gkm502. PMC 2018635. PMID 17704138.
  9. ↑ Whitehouse, C J; Taylor R M; Thistlethwaite A; Zhang H; Karimi-Busheri F; Lasko D D; Weinfeld M; Caldecott K W (Jan 2001). "XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair". Cell (United States) 104 (1): 107–17. doi:10.1016/S0092-8674(01)00195-7. ISSN 0092-8674. PMID 11163244.
  10. ↑ Wang, Liming; Bhattacharyya Nandan; Chelsea Diane M; Escobar Pedro F; Banerjee Sipra (Nov 2004). "A novel nuclear protein, MGC5306 interacts with DNA polymerase beta and has a potential role in cellular phenotype". Cancer Res. (United States) 64 (21): 7673–7. doi:10.1158/0008-5472.CAN-04-2801. ISSN 0008-5472. PMID 15520167.
  11. ↑ Fan, Jinshui; Otterlei Marit; Wong Heng-Kuan; Tomkinson Alan E; Wilson David M (2004). "XRCC1 co-localizes and physically interacts with PCNA". Nucleic Acids Res. (England) 32 (7): 2193–201. doi:10.1093/nar/gkh556. PMC 407833. PMID 15107487.
  12. ↑ Kubota, Y; Nash R A; Klungland A; Schär P; Barnes D E; Lindahl T (Dec 1996). "Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein". EMBO J. (ENGLAND) 15 (23): 6662–70. ISSN 0261-4189. PMC 452490. PMID 8978692.
  13. ↑ Bhattacharyya, N; Banerjee S (Jul 2001). "A novel role of XRCC1 in the functions of a DNA polymerase beta variant". Biochemistry (United States) 40 (30): 9005–13. doi:10.1021/bi0028789. ISSN 0006-2960. PMID 11467963.

Further reading

External links