DNA polymerase beta

Details

Name
DNA polymerase beta
Kind
protein
Synonyms
  • 2.7.7.7
  • 5'-deoxyribose-phosphate lyase
  • 5'-dRP lyase
  • AP lyase
Gene Name
POLB
UniProtKB Entry
P06746Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0018921|DNA polymerase beta
MSKRKAPQETLNGGITDMLTELANFEKNVSQAIHKYNAYRKAASVIAKYPHKIKSGAEAK
KLPGVGTKIAEKIDEFLATGKLRKLEKIRQDDTSSSINFLTRVSGIGPSAARKFVDEGIK
TLEDLRKNEDKLNHHQRIGLKYFGDFEKRIPREEMLQMQDIVLNEVKKVDSEYIATVCGS
FRRGAESSGDMDVLLTHPSFTSESTKQPKLLHQVVEQLQKVHFITDTLSKGETKFMGVCQ
LPSKNDEKEYPHRRIDIRLIPKDQYYCGVLYFTGSDIFNKNMRAHALEKGFTINEYTIRP
LGVTGVAGEPLPVDSEKDIFDYIQWKYREPKDRSE
Number of residues
335
Molecular Weight
38177.34
Theoretical pI
9.41
GO Classification
Functions
5'-deoxyribose-5-phosphate lyase activity / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) endonuclease activity
Processes
DNA damage response / DNA-templated DNA replication / double-strand break repair via nonhomologous end joining / in utero embryonic development
Components
protein-containing complex
General Function
Repair polymerase that plays a key role in base-excision repair (PubMed:10556592, PubMed:9207062, PubMed:9572863). During this process, the damaged base is excised by specific DNA glycosylases, the DNA backbone is nicked at the abasic site by an apurinic/apyrimidic (AP) endonuclease, and POLB removes 5'-deoxyribose-phosphate from the preincised AP site acting as a 5'-deoxyribose-phosphate lyase (5'-dRP lyase); through its DNA polymerase activity, it adds one nucleotide to the 3' end of the arising single-nucleotide gap (PubMed:10556592, PubMed:17526740, PubMed:9556598, PubMed:9572863, PubMed:9614142). Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases. It is also able to cleave sugar-phosphate bonds 3' to an intact AP site, acting as an AP lyase (PubMed:9614142)
Specific Function
5'-deoxyribose-5-phosphate lyase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0018922|DNA polymerase beta (POLB)
ATGAGCAAACGGAAGGCGCCGCAGGAGACTCTCAACGGGGGAATCACCGACATGCTCACA
GAACTCGCAAACTTTGAGAAGAACGTGAGCCAAGCTATCCACAAGTACAATGCTTACAGA
AAAGCAGCATCTGTTATAGCAAAATACCCACACAAAATAAAGAGTGGAGCTGAAGCTAAG
AAATTGCCTGGAGTAGGAACAAAAATTGCTGAAAAGATTGATGAGTTTTTAGCAACTGGA
AAATTACGTAAACTGGAAAAGATTCGGCAGGATGATACGAGTTCATCCATCAATTTCCTG
ACTCGAGTTAGTGGCATTGGTCCATCTGCTGCAAGGAAGTTTGTAGATGAAGGAATTAAA
ACACTAGAAGATCTCAGAAAAAATGAAGATAAATTGAACCATCATCAGCGAATTGGGCTG
AAATATTTTGGGGACTTTGAAAAAAGAATTCCTCGTGAAGAGATGTTACAAATGCAAGAT
ATTGTACTAAATGAAGTTAAAAAAGTGGATTCTGAATACATTGCTACAGTCTGTGGCAGT
TTCAGAAGAGGTGCAGAGTCCAGTGGTGACATGGATGTTCTCCTGACCCATCCCAGCTTC
ACTTCAGAATCAACCAAACAGCCAAAACTGTTACATCAGGTTGTGGAGCAGTTACAAAAG
GTTCATTTTATCACAGATACCCTGTCAAAGGGTGAGACAAAGTTCATGGGTGTTTGCCAG
CTTCCCAGTAAAAATGATGAAAAAGAATATCCACACAGAAGAATTGATATCAGGTTGATA
CCCAAAGATCAGTATTACTGTGGTGTTCTCTATTTCACTGGGAGTGATATTTTCAATAAG
AATATGAGGGCTCATGCCCTAGAAAAGGGTTTCACAATCAATGAGTACACCATCCGTCCC
TTGGGAGTCACTGGAGTTGCAGGAGAACCCCTGCCAGTGGATAGTGAAAAAGACATCTTT
GATTACATCCAGTGGAAATACCGGGAACCCAAGGACCGGAGCGAATGA
Chromosome Location
8
Locus
8p11.21
External Identifiers
ResourceLink
UniProtKB IDP06746
UniProtKB Entry NameDPOLB_HUMAN
GenBank Protein ID292397
GenBank Gene IDL11607
GeneCard IDPOLB
GenAtlas IDPOLB
HGNC IDHGNC:9174
PDB ID(s)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, 4YMM, 4YMN, 4YMO, 4YN4, 4Z6C, 4Z6D, 4Z6E, 4Z6F, 5BOL, 5BOM, 5BPC, 5DB6, 5DB7, 5DB8, 5DB9, 5DBA, 5DBB, 5DBC, 5EOZ, 5HHH, 5HHI, 5J0O, 5J0P, 5J0Q, 5J0R, 5J0S, 5J0T, 5J0U, 5J0W, 5J0X, 5J0Y, 5J29, 5J2A, 5J2B, 5J2C, 5J2D, 5J2E, 5J2F, 5J2G, 5J2H, 5J2I, 5J2J, 5J2K, 5TB8, 5TB9, 5TBA, 5TBB, 5TBC, 5TZV, 5U2R, 5U2S, 5U2T, 5U8G, 5U8H, 5U8I, 5U9H, 5UGN, 5UGO, 5UGP, 5V1F, 5V1G, 5V1H, 5V1I, 5V1J, 5V1N, 5V1O, 5V1P, 5V1R, 5VEZ, 5VRW, 5VRX, 5VRY, 5VRZ, 5VS0, 5VS1, 5VS2, 5VS3, 5VS4, 5WNX, 5WNY, 5WNZ, 5WO0, 6BEL, 6BEM, 6BTE, 6BTF, 6CLY, 6CPQ, 6CR3, 6CR4, 6CR5, 6CR6, 6CR7, 6CR8, 6CR9, 6CRB, 6CRC, 6CRH, 6CTI, 6CTJ, 6CTK, 6CTL, 6CTM, 6CTN, 6CTO, 6CTP, 6CTQ, 6CTR, 6CTT, 6CTU, 6CTV, 6CTW, 6CTX, 6CU9, 6CUA, 6CUB, 6DIA, 6DIC, 6E3R, 6E3V, 6E3W, 6E3X, 6G2Q, 6MR7, 6MR8, 6N2R, 6N2S, 6N2T, 6NKR, 6NKS, 6NKT, 6NKU, 6NKV, 6NKW, 6NKX, 6NKY, 6NKZ, 6NL0, 6PH5, 6PH6, 6PKZ, 6U2O, 6U6B, 6UOK, 6UOL, 6UOM, 6W2M, 7ICE, 7ICF, 7ICG, 7ICH, 7ICI, 7ICJ, 7ICK, 7ICL, 7ICM, 7ICN, 7ICO, 7ICP, 7ICQ, 7ICR, 7ICS, 7ICT, 7ICU, 7ICV, 7K96, 7K97, 7MZ0, 7MZ1, 7MZ2, 7MZ3, 7MZ4, 7MZ8, 7RBE, 7RBF, 7RBG, 7RBH, 7RBI, 7RBJ, 7RBK, 7RBL, 7RBM, 7RBN, 7RBO, 7S9J, 7S9K, 7S9L, 7S9M, 7S9N, 7S9O, 7S9P, 7S9Q, 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
KEGG IDhsa:5423
IUPHAR/Guide To Pharmacology ID3231
NCBI Gene ID5423
General References
  1. Patterson TA, Little W, Cheng X, Widen SG, Kumar A, Beard WA, Wilson SH: Molecular cloning and high-level expression of human polymerase beta cDNA and comparison of the purified recombinant human and rat enzymes. Protein Expr Purif. 2000 Feb;18(1):100-10. [Article]
  2. Dobashi Y, Kubota Y, Shuin T, Torigoe S, Yao M, Hosaka M: Polymorphisms in the human DNA polymerase beta gene. Hum Genet. 1995 Apr;95(4):389-90. [Article]
  3. Chyan YJ, Ackerman S, Shepherd NS, McBride OW, Widen SG, Wilson SH, Wood TG: The human DNA polymerase beta gene structure. Evidence of alternative splicing in gene expression. Nucleic Acids Res. 1994 Jul 25;22(14):2719-25. [Article]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Widen SG, Kedar P, Wilson SH: Human beta-polymerase gene. Structure of the 5'-flanking region and active promoter. J Biol Chem. 1988 Nov 15;263(32):16992-8. [Article]
  7. Abbotts J, SenGupta DN, Zmudzka B, Widen SG, Notario V, Wilson SH: Expression of human DNA polymerase beta in Escherichia coli and characterization of the recombinant enzyme. Biochemistry. 1988 Feb 9;27(3):901-9. [Article]
  8. SenGupta DN, Zmudzka BZ, Kumar P, Cobianchi F, Skowronski J, Wilson SH: Sequence of human DNA polymerase beta mRNA obtained through cDNA cloning. Biochem Biophys Res Commun. 1986 Apr 14;136(1):341-7. [Article]
  9. Bennett RA, Wilson DM 3rd, Wong D, Demple B: Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-9. [Article]
  10. Matsumoto Y, Kim K, Katz DS, Feng JA: Catalytic center of DNA polymerase beta for excision of deoxyribose phosphate groups. Biochemistry. 1998 May 5;37(18):6456-64. [Article]
  11. DeMott MS, Beyret E, Wong D, Bales BC, Hwang JT, Greenberg MM, Demple B: Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone. J Biol Chem. 2002 Mar 8;277(10):7637-40. Epub 2002 Jan 22. [Article]
  12. El-Andaloussi N, Valovka T, Toueille M, Steinacher R, Focke F, Gehrig P, Covic M, Hassa PO, Schar P, Hubscher U, Hottiger MO: Arginine methylation regulates DNA polymerase beta. Mol Cell. 2006 Apr 7;22(1):51-62. [Article]
  13. Parsons JL, Tait PS, Finch D, Dianova II, Edelmann MJ, Khoronenkova SV, Kessler BM, Sharma RA, McKenna WG, Dianov GL: Ubiquitin ligase ARF-BP1/Mule modulates base excision repair. EMBO J. 2009 Oct 21;28(20):3207-15. doi: 10.1038/emboj.2009.243. Epub 2009 Aug 27. [Article]
  14. Parsons JL, Dianova II, Khoronenkova SV, Edelmann MJ, Kessler BM, Dianov GL: USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase beta. Mol Cell. 2011 Mar 4;41(5):609-15. doi: 10.1016/j.molcel.2011.02.016. [Article]
  15. Pelletier H, Sawaya MR, Wolfle W, Wilson SH, Kraut J: A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase beta. Biochemistry. 1996 Oct 1;35(39):12762-77. [Article]
  16. Pelletier H, Sawaya MR: Characterization of the metal ion binding helix-hairpin-helix motifs in human DNA polymerase beta by X-ray structural analysis. Biochemistry. 1996 Oct 1;35(39):12778-87. [Article]
  17. Sawaya MR, Prasad R, Wilson SH, Kraut J, Pelletier H: Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: evidence for an induced fit mechanism. Biochemistry. 1997 Sep 16;36(37):11205-15. [Article]
  18. Krahn JM, Beard WA, Miller H, Grollman AP, Wilson SH: Structure of DNA polymerase beta with the mutagenic DNA lesion 8-oxodeoxyguanine reveals structural insights into its coding potential. Structure. 2003 Jan;11(1):121-7. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Cytarabineapproved, investigationalyestargetinhibitorDetails
dATPexperimentalunknowntargetDetails
(1S)-1,2,3,4-TETRAHYDRO-BENZO[C]PHENANTHRENE-2,3,4-TRIOLexperimentalunknowntargetDetails
IronapprovedunknowntargetDetails
Ferrous gluconateapprovedunknowntargetDetails
Ferrous succinateapprovedunknowntargetDetails
Ferrous ascorbateapprovedunknowntargetDetails
Ferrous fumarateapprovedunknowntargetDetails
Ferrous glycine sulfateapprovedunknowntargetDetails
4'-Thio-facinvestigationalyestargetinhibitorDetails
Brincidofovirapproved, investigationalyestargetinhibitorDetails