DNA Polymerase Iota

For other uses, see Poli (disambiguation).

POLI
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1T3N, 1ZET, 2ALZ, 2DPI, 2DPJ, 2FLL, 2FLN, 2FLP, 2KHU, 2KHW, 2KTF, 2L0G, 2MBB, 3EPG, 3EPI, 3G6X, 3G6Y, 3GV5, 3GV7, 3GV8, 3H40, 3H4B, 3H4D, 3NGD, 3OSN, 3Q8P, 3Q8Q, 3Q8R, 3Q8S, 4EBC, 4EBD, 4EBE, 4EYH, 4EYI, 4FS1, 4FS2
Identifiers
Aliases	POLI , RAD30B, RAD3OB, polymerase (DNA) iota, DNA polymerase iota
External IDs	OMIM: 605252; MGI: 1347081; HomoloGene: 5209; GeneCards: POLI; OMA:POLI - orthologs
Gene location (Mouse) Chr. Chromosome 18 (mouse) [1] Band 18 44.48 cM|18 E2 Start 70,641,751 bp [1] End 70,663,691 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in seminiferous tubule spermatid zygote spermatocyte blood tail of embryo Pituitary Gland yolk sac spleen secondary oocyte BioGPS More reference expression data
Gene ontology Molecular function transferase activity damaged DNA binding DNA-directed DNA polymerase activity DNA binding nucleotidyltransferase activity protein binding metal ion binding Cellular component intracellular anatomical structure nucleoplasm nucleus nuclear speck cytoplasmic ribonucleoprotein granule Biological process DNA replication translesion synthesis DNA biosynthetic process DNA repair error-prone translesion synthesis cellular response to DNA damage stimulus Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11201 26447 Ensembl ENSG00000101751 ENSMUSG00000038425 UniProt Q9UNA4 Q6R3M4 RefSeq (mRNA) NM_007195 NM_001136090 NM_001289515 NM_001289516 NM_011972 RefSeq (protein) NP_009126 NP_001338539 NP_001338540 NP_001338541 NP_001338542 NP_001338543 NP_001338544 NP_001338545 NP_001338546 NP_001338547 NP_001338548 NP_001338549 NP_001338550 NP_001338561 NP_001129562 NP_001276444 NP_001276445 NP_036102 NP_001390096 NP_001390097 NP_001390098 NP_001390102 NP_001390103 NP_001390104 NP_001390106 NP_001390108 NP_001390112 NP_001390118 Location (UCSC) n/a Chr 18: 70.64 – 70.66 Mb PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

DNA polymerase iota is an enzyme that in humans is encoded by the POLI gene. ^[4] It is found in higher eukaryotes, and is believed to have arisen from a gene duplication from Pol η. Pol ι, is a Y family polymerase that is involved in translesion synthesis. It can bypass 6-4 pyrimidine adducts and abasic sites and has a high frequency of wrong base incorporation. Like many other Y family polymerases Pol ι, has low processivity, a large DNA binding pocket and doesn't undergo conformational changes when DNA binds. These attributes are what allow Pol ι to carry out its task as a translesion polymerase. Pol ι only uses Hoogsteen base pairing, during DNA synthesis, it will add adenine opposite to thymine in the syn conformation and can add both cytosine and thymine in the anti conformation across guanine, which it flips to the syn conformation.

Xeroderma pigmentosum variant

Xeroderma pigmentosum variant (XPV) cells lack DNA polymerase eta (η). ^[5] Instead these cells use DNA polymerase iota (ι). ^[5] Exposure of XPV cells to UV light causes a very high frequency and unique spectrum of UV-induced mutations that can ultimately lead to malignant transformation. ^[5]

References

1. GRCm38: Ensembl release 89: ENSMUSG00000038425 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Frank EG, Woodgate R (Aug 2007). "Increased catalytic activity and altered fidelity of human DNA polymerase iota in the presence of manganese". J Biol Chem. 282 (34): 24689–96. doi: 10.1074/jbc.M702159200 . PMID   17609217.
5. Wang Y, Woodgate R, McManus TP, Mead S, McCormick JJ, Maher VM. Evidence that in xeroderma pigmentosum variant cells, which lack DNA polymerase eta, DNA polymerase iota causes the very high frequency and unique spectrum of UV-induced mutations. Cancer Res. 2007 Apr 1;67(7):3018-26. doi: 10.1158/0008-5472.CAN-06-3073. PMID: 17409408

Further reading

• McIntyre J (2020). "Polymerase iota - an odd sibling among Y family polymerases". DNA Repair. 86 (102753): 102753. doi: 10.1016/j.dnarep.2019.102753 . PMID   31805501.
• McDonald JP, Tissier A, Frank EG, et al. (2001). "DNA polymerase iota and related rad30-like enzymes". Philos. Trans. R. Soc. Lond. B Biol. Sci. 356 (1405): 53–60. doi:10.1098/rstb.2000.0748. PMC   1087691 . PMID   11205331.
• Tissier A, Frank EG, McDonald JP, et al. (2001). "Biochemical characterization of human DNA polymerase iota provides clues to its biological function". Biochem. Soc. Trans. 29 (Pt 2): 183–7. doi:10.1042/BST0290183. PMID   11356150.
• McDonald JP, Rapić-Otrin V, Epstein JA, et al. (1999). "Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta". Genomics. 60 (1): 20–30. doi:10.1006/geno.1999.5906. PMID   10458907.
• Masutani C, Kusumoto R, Iwai S, Hanaoka F (2000). "Mechanisms of accurate translesion synthesis by human DNA polymerase eta". EMBO J. 19 (12): 3100–9. doi:10.1093/emboj/19.12.3100. PMC   203367 . PMID   10856253.
• Tissier A, McDonald JP, Frank EG, Woodgate R (2000). "poliota, a remarkably error-prone human DNA polymerase". Genes Dev. 14 (13): 1642–50. doi:10.1101/gad.14.13.1642. PMC   316739 . PMID   10887158.
• Tissier A, Frank EG, McDonald JP, et al. (2000). "Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota". EMBO J. 19 (19): 5259–66. doi:10.1093/emboj/19.19.5259. PMC   302107 . PMID   11013228.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Bebenek K, Tissier A, Frank EG, et al. (2001). "5'-Deoxyribose phosphate lyase activity of human DNA polymerase iota in vitro". Science. 291 (5511): 2156–9. Bibcode:2001Sci...291.2156B. doi:10.1126/science.1058386. PMID   11251121. S2CID   83716303.
• Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC   1083732 . PMID   11256614.
• Frank EG, Tissier A, McDonald JP, et al. (2001). "Altered nucleotide misinsertion fidelity associated with poliota-dependent replication at the end of a DNA template". EMBO J. 20 (11): 2914–22. doi:10.1093/emboj/20.11.2914. PMC   125476 . PMID   11387224.
• Vaisman A, Tissier A, Frank EG, et al. (2001). "Human DNA polymerase iota promiscuous mismatch extension". J. Biol. Chem. 276 (33): 30615–22. doi: 10.1074/jbc.M102694200 . PMID   11402031.
• Ohmori H, Friedberg EC, Fuchs RP, et al. (2001). "The Y-family of DNA polymerases". Mol. Cell. 8 (1): 7–8. doi: 10.1016/S1097-2765(01)00278-7 . PMID   11515498.
• Vaisman A, Woodgate R (2002). "Unique misinsertion specificity of poliota may decrease the mutagenic potential of deaminated cytosines". EMBO J. 20 (22): 6520–9. doi:10.1093/emboj/20.22.6520. PMC   125734 . PMID   11707422.
• Faili A, Aoufouchi S, Flatter E, et al. (2002). "Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota". Nature. 419 (6910): 944–7. Bibcode:2002Natur.419..944F. doi:10.1038/nature01117. PMID   12410315. S2CID   4431410.
• Kannouche P, Fernández de Henestrosa AR, Coull B, et al. (2003). "Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells". EMBO J. 21 (22): 6246–56. doi:10.1093/emboj/cdf618. PMC   137208 . PMID   12426396.
• Frank EG, Sayer JM, Kroth H, et al. (2002). "Translesion replication of benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxyadenosine and deoxyguanosine by human DNA polymerase iota". Nucleic Acids Res. 30 (23): 5284–92. doi:10.1093/nar/gkf643. PMC   137958 . PMID   12466554.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.