DNK polimeraza beta

Regulatorni element u POLB
	Predviđena sekundarna struktura stem loopII (M2) regulatornog elementa POLB
Identifikatori
Simbol	POLB
Rfam	RF01455
Entrez	5423
HUGO	POLB
OMIM	174760
RefSeq	NM_002690
	Drugi podaci
RNK tip	Cis-reg
Domain(i)	Mammalia
Lokus	Hromozom 8 p11.2

DNK polimeraza beta
	; PDB prikaz baziran na 1bno.
Dostupne strukture
	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, 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
Identifikatori
Simboli	POLB; MGC125976
Vanjski ID	OMIM: 174760 MGI: 97740 HomoloGene: 2013 GeneCards: POLB Gene
EC broj	2.7.7.7
Ontologija gena
Molekularna funkcija	• vezivanje oštećene DNK; • aktivnost DNK-usmerene DNK polimeraze; • proteinsko vezivanje; • vezivanje mikrotubula; • aktivnost transferaze; • aktivnosti nukleotidiltransferaze; • aktivnost liaze; • vezivanje enzima; • vezivanje metalnog jona;
Celularna komponenta	• nukleus; • nukleoplazma; • citoplazma; • mikrotubula; • vreteno mikrotubule;
Biološki proces	• DNK-zavisna DNK replikacija; • DNK popravka; • popravka ekscizije baza; • popravka pirimidinskog dimera; • popravka nukleotidne ekscizije, popunjavanje DNK praznina; • anti apoptoza; • respons na DNK oštećenja; • ćelijska smrt; • respons na etanol;
Pregled RNK izražavanja
	podaci
Ortolozi

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DNK polimeraza beta (POLB) je enzim koji kod ljudi kodira POLB gen.^[1]

Funkcija uredi

U eukariotskim ćelijama, DNK polimeraza beta (POLB) izvodi popravke ekscizijom baza (BER) koje su neophodne za popravku DNK, replikaciju, rekombinaciju, i otpornost na lekove.^[1]

Regulacija ekspresije uredi

DNK polimeraza beta održava genomski integritet putem uzimanja učešća u popravci ekscizijom baza. Prekomerno izražavanje POLB iRNK je u korelaciji sa brojnim tipovima kancera, dok deficijencije POLB-a rezultuju u hipersenzitivnosti na alkilirajuće agense, uključujući apoptozu, i prekid hromozoma.^[2] Iz tih razloga, esencijalno je precizno održavanje kontrole POLB ekspresije.^[3]^[4]^[5]^[6]

Interakcije uredi

DNA polimeraza beta formira interakcije sa PNKP^[7] i XRCC1.^[8]^[9]^[10]^[11]

Reference uredi

↑ ^1,0 ^1,1 „Entrez Gene: POLB polymerase (DNA directed), beta”.
↑ 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.
↑ Canitrot Y, Cazaux C, Fréchet M i dr.. (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.
↑ Bergoglio V, Pillaire MJ, Lacroix-Triki M i dr.. (June 2002). „Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis”. Cancer Res. 62 (12): 3511–4. PMID 12067997.
↑ Bergoglio V, Canitrot Y, Hogarth L i dr.. (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.
↑ 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.
↑ Whitehouse, C J; Taylor R M, Thistlethwaite A, Zhang H, Karimi-Busheri F, Lasko D D, Weinfeld M, Caldecott K W (January 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.
↑ Wang, Liming; Bhattacharyya Nandan, Chelsea Diane M, Escobar Pedro F, Banerjee Sipra (November 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.
↑ 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.
↑ Kubota, Y; Nash R A, Klungland A, Schär P, Barnes D E, Lindahl T (December 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.
↑ Bhattacharyya, N; Banerjee S (July 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.

Literatura uredi

Date T, Tanihara K, Yamamoto S i dr.. (1992). „Two regions in human DNA polymerase beta mRNA suppress translation in Escherichia coli”. Nucleic Acids Res. 20 (18): 4859–64. DOI:10.1093/nar/20.18.4859. PMC 334243. PMID 1408801.
Wang L, Patel U, Ghosh L, Banerjee S (1992). „DNA polymerase beta mutations in human colorectal cancer”. Cancer Res. 52 (17): 4824–7. PMID 1511447.
Tokui T, Inagaki M, Nishizawa K i dr.. (1991). „Inactivation of DNA polymerase beta by in vitro phosphorylation with protein kinase C”. J. Biol. Chem. 266 (17): 10820–4. PMID 2040602.
SenGupta DN, Zmudzka BZ, Kumar P i dr.. (1986). „Sequence of human DNA polymerase beta mRNA obtained through cDNA cloning”. Biochem. Biophys. Res. Commun. 136 (1): 341–7. DOI:10.1016/0006-291X(86)90916-2. PMID 2423078.
Zmudzka BZ, Fornace A, Collins J, Wilson SH (1988). „Characterization of DNA polymerase beta mRNA: cell-cycle and growth response in cultured human cells”. Nucleic Acids Res. 16 (20): 9587–96. DOI:10.1093/nar/16.20.9587. PMC 338765. PMID 2460824.
Widen SG, Kedar P, Wilson SH (1988). „Human beta-polymerase gene. Structure of the 5'-flanking region and active promoter”. J. Biol. Chem. 263 (32): 16992–8. PMID 3182828.
Abbotts J, SenGupta DN, Zmudzka B i dr.. (1988). „Expression of human DNA polymerase beta in Escherichia coli and characterization of the recombinant enzyme”. Biochemistry 27 (3): 901–9. DOI:10.1021/bi00403a010. PMID 3284575.
Dobashi Y, Kubota Y, Shuin T i dr.. (1995). „Polymorphisms in the human DNA polymerase beta gene”. Hum. Genet. 95 (4): 389–90. PMID 7705833.
Chyan YJ, Ackerman S, Shepherd NS i dr.. (1994). „The human DNA polymerase beta gene structure. Evidence of alternative splicing in gene expression”. Nucleic Acids Res. 22 (14): 2719–25. DOI:10.1093/nar/22.14.2719. PMC 308239. PMID 7914364.
Maruyama K, Sugano S (1994). „Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides”. Gene 138 (1–2): 171–4. DOI:10.1016/0378-1119(94)90802-8. PMID 8125298.
Chang M, Burmer GC, Sweasy J i dr.. (1994). „Evidence against DNA polymerase beta as a candidate gene for Werner syndrome”. Hum. Genet. 93 (5): 507–12. PMID 8168825.
Chyan YJ, Strauss PR, Wood TG, Wilson SH (1996). „Identification of novel mRNA isoforms for human DNA polymerase beta”. DNA Cell Biol. 15 (8): 653–9. DOI:10.1089/dna.1996.15.653. PMID 8769567.
Pelletier H, Sawaya MR, Wolfle W i dr.. (1996). „Crystal structures of human DNA polymerase beta complexed with DNA: implications for catalytic mechanism, processivity, and fidelity”. Biochemistry 35 (39): 12742–61. DOI:10.1021/bi952955d. PMID 8841118.
Pelletier H, Sawaya MR, Wolfle W i dr.. (1996). „A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase beta”. Biochemistry 35 (39): 12762–77. DOI:10.1021/bi9529566. PMID 8841119.
Pelletier H, Sawaya MR (1996). „Characterization of the metal ion binding helix-hairpin-helix motifs in human DNA polymerase beta by X-ray structural analysis”. Biochemistry 35 (39): 12778–87. DOI:10.1021/bi960790i. PMID 8841120.
Kubota Y, Nash RA, Klungland A i dr.. (1997). „Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein”. EMBO J. 15 (23): 6662–70. PMC 452490. PMID 8978692.
Bennett RA, Wilson DM, Wong D, Demple B (1997). „Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway”. Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7166–9. DOI:10.1073/pnas.94.14.7166. PMC 23779. PMID 9207062.
Sawaya MR, Prasad R, Wilson SH i dr.. (1997). „Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: evidence for an induced fit mechanism”. Biochemistry 36 (37): 11205–15. DOI:10.1021/bi9703812. PMID 9287163.
Bhattacharyya N, Banerjee S (1997). „A variant of DNA polymerase beta acts as a dominant negative mutant”. Proc. Natl. Acad. Sci. U.S.A. 94 (19): 10324–9. DOI:10.1073/pnas.94.19.10324. PMC 23361. PMID 9294209.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K i dr.. (1997). „Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library”. Gene 200 (1–2): 149–56. DOI:10.1016/S0378-1119(97)00411-3. PMID 9373149.

Vidi još uredi

POLA1
POLA2

Spoljašnje veze uredi

Rfam entry for the stem loopII (M2) regulatory element in POLB^{[mrtav link]}

[entrez-1] 1,0 ^1,1 „Entrez Gene: POLB polymerase (DNA directed), beta”.

[pmid8702497-2] 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.

[pmid9770529-3] Canitrot Y, Cazaux C, Fréchet M i dr.. (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.

[pmid12067997-4] Bergoglio V, Pillaire MJ, Lacroix-Triki M i dr.. (June 2002). „Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis”. Cancer Res. 62 (12): 3511–4. PMID 12067997.

[pmid11593426-5] Bergoglio V, Canitrot Y, Hogarth L i dr.. (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.

[pmid10357787-6] 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.

[pmid11163244-7] Whitehouse, C J; Taylor R M, Thistlethwaite A, Zhang H, Karimi-Busheri F, Lasko D D, Weinfeld M, Caldecott K W (January 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.

[pmid15520167-8] Wang, Liming; Bhattacharyya Nandan, Chelsea Diane M, Escobar Pedro F, Banerjee Sipra (November 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.

[pmid15107487-9] 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.

[pmid8978692-10] Kubota, Y; Nash R A, Klungland A, Schär P, Barnes D E, Lindahl T (December 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.

[pmid11467963-11] Bhattacharyya, N; Banerjee S (July 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.

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