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POLK  -  polymerase (DNA directed) kappa

Homo sapiens

Synonyms: DINB protein, DINB1, DINP, DNA polymerase kappa, POLQ
 
 
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Disease relevance of POLK

  • BYRON POLK STOOKEY, an outstanding clinician and teacher, served as Director and Chief of Neurosurgery at the Neurological Institute of New York Columbia-Presbyterian Medical Center. Highlights of his clinical contributions include improved peripheral nerve and spine surgery and subtemporal trigeminal nerve section for tic douloureux [1].
  • To investigate whether POLK expression might be regulated by p53, we have determined the transcriptional initiation site of POLK gene and examined its promoter activity in A549, H358-129, and PC-3 human lung cancer cell lines [2].
  • These include human DNA polymerase kappa (pol kappa), a homologue of Escherichia coli pol IV, which enhances the frequency of spontaneous mutation [3].
  • RESULTS: The prevalence of HIV infection was 5.3% overall but was highly stratified by gender and sexual preference (15.6% among homosexual/bisexual men vs. heterosexual men) and recruitment neighborhood (18% in the Polk Street area) [4].
  • From February through December 1978, venereal disease casefinders in Polk County, Iowa used an expanded interview period of at least 120 days to interview 983 gonorrhea patients for sexual partner information [5].
 

High impact information on POLK

 

Chemical compound and disease context of POLK

 

Biological context of POLK

 

Anatomical context of POLK

  • Multiple PolK (POLK) transcripts in mammalian testis [16].
  • In addition, POLK promoter exhibited a significantly higher activity in p53-/- murine embryo fibroblasts (MEF) than in p53+/- and p53+/+ MEF [2].
  • The effects of the peroxisome proliferators di-isononyl phthalate (DINP) and di-2-ethylhexyl phthalate (DEHP) were evaluated in young adult male cynomolgus monkeys after 14 days of treatment, with emphasis on detecting hepatic and other effects seen in rats and mice after treatment with high doses of phthalates [11].
  • When orally administered to rodents, DINP is rapidly metabolized in the gastrointestinal tract to the corresponding monoester, absorbed and excreted, primarily in the urine [17].
 

Associations of POLK with chemical compounds

  • No effect was observed for bis-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP), whereas dibutyl phthalate (DBP) appeared to down-regulate hNIS promoter [18].
  • Groups of 4 monkeys received DINP (500 mg/kg/day), DEHP (500 mg/kg/day), or vehicle (0.5% methyl cellulose, 10 ml/kg) by intragastric intubation for 14 consecutive days [11].
  • Additionally, in situ dye transfer studies using fresh liver slices revealed that DINP, DEHP, and clofibrate had no effect on gap junctional intercellular communication (GJIC) [11].
  • Studies with di(2-ethylhexyl) (DEHP) and diisononyl (DINP) phthalates demonstrated that inhibition of GJIC in rats and mice was well correlated with induction of both liver tumors and markers for peroxisomal proliferation [19].
  • Di-isononyl phthalate (DINP; CAS no. 68515-48-0) is a general-purpose plasticizer for polyvinyl chloride [17].
 

Other interactions of POLK

  • Wild-type p53, but not a mutant p53 (R273H) devoid of the DNA-binding activity, strongly inhibited POLK promoter activity in these cells [2].
 

Analytical, diagnostic and therapeutic context of POLK

  • Using RT-PCR to amplify the coding sequence of the PolK gene, 11 forms of mouse PolK and 5 forms of human POLK transcripts were identified from testis [16].
  • Polk, Jr, M.D., the Trauma Service has received national recognition for excellence in patient care and surgical research [20].
  • To assist in understanding the basis for these species differences, the pharmacokinetic properties of DINP were evaluated in rodents following both oral and dermal administration [17].
  • The current multimodality treatment of intraabdominal infections is based upon the fundamental principles established by Polk in 1979: surgical source control, fluid resuscitation, adequate nutrition, support of failing organ systems, and antibiotics [21].

References

  1. Byron Stookey: "the old lion"--an unsung giant of neurosurgery. Kaufman, H.H., Goodrich, J.T. Neurosurgery (1997) [Pubmed]
  2. Elevated expression of DNA polymerase kappa in human lung cancer is associated with p53 inactivation: Negative regulation of POLK promoter activity by p53. Wang, Y., Seimiya, M., Kawamura, K., Yu, L., Ogi, T., Takenaga, K., Shishikura, T., Nakagawara, A., Sakiyama, S., Tagawa, M., O-Wang, J. Int. J. Oncol. (2004) [Pubmed]
  3. Translesion synthesis by human DNA polymerase kappa on a DNA template containing a single stereoisomer of dG-(+)- or dG-(-)-anti-N(2)-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene). Suzuki, N., Ohashi, E., Kolbanovskiy, A., Geacintov, N.E., Grollman, A.P., Ohmori, H., Shibutani, S. Biochemistry (2002) [Pubmed]
  4. Prevalence and correlates of HIV infection among young injection drug users in San Francisco. Shafer, K.P., Hahn, J.A., Lum, P.J., Ochoa, K., Graves, A., Moss, A. J. Acquir. Immune Defic. Syndr. (2002) [Pubmed]
  5. Establishing efficient interview periods for gonorrhea patients. Starcher, E.T., Kramer, M.A., Carlota-Orduna, B., Lundberg, D.F. American journal of public health. (1983) [Pubmed]
  6. Error-prone bypass of certain DNA lesions by the human DNA polymerase kappa. Ohashi, E., Ogi, T., Kusumoto, R., Iwai, S., Masutani, C., Hanaoka, F., Ohmori, H. Genes Dev. (2000) [Pubmed]
  7. Human and mouse homologs of Escherichia coli DinB (DNA polymerase IV), members of the UmuC/DinB superfamily. Gerlach, V.L., Aravind, L., Gotway, G., Schultz, R.A., Koonin, E.V., Friedberg, E.C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  8. DNA polymerase kappa is specifically required for recovery from the benzo[a]pyrene-dihydrodiol epoxide (BPDE)-induced S-phase checkpoint. Bi, X., Slater, D.M., Ohmori, H., Vaziri, C. J. Biol. Chem. (2005) [Pubmed]
  9. Human DNA polymerase kappa bypasses and extends beyond thymine glycols during translesion synthesis in vitro, preferentially incorporating correct nucleotides. Fischhaber, P.L., Gerlach, V.L., Feaver, W.J., Hatahet, Z., Wallace, S.S., Friedberg, E.C. J. Biol. Chem. (2002) [Pubmed]
  10. Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product of the human DINB1 gene. Ohashi, E., Bebenek, K., Matsuda, T., Feaver, W.J., Gerlach, V.L., Friedberg, E.C., Ohmori, H., Kunkel, T.A. J. Biol. Chem. (2000) [Pubmed]
  11. Effects of di-isononyl phthalate, di-2-ethylhexyl phthalate, and clofibrate in cynomolgus monkeys. Pugh, G., Isenberg, J.S., Kamendulis, L.M., Ackley, D.C., Clare, L.J., Brown, R., Lington, A.W., Smith, J.H., Klaunig, J.E. Toxicol. Sci. (2000) [Pubmed]
  12. Error-prone and inefficient replication across 8-hydroxyguanine (8-oxoguanine) in human and mouse ras gene fragments by DNA polymerase kappa. Jałoszyński, P., Ohashi, E., Ohmori, H., Nishimura, S. Genes Cells (2005) [Pubmed]
  13. Adaptation to DNA damage and stimulation of genetic instability: the double-edged sword mammalian DNA polymerase kappa. Bavoux, C., Hoffmann, J.S., Cazaux, C. Biochimie (2005) [Pubmed]
  14. Crystal structure of the catalytic core of human DNA polymerase kappa. Uljon, S.N., Johnson, R.E., Edwards, T.A., Prakash, S., Prakash, L., Aggarwal, A.K. Structure (Camb.) (2004) [Pubmed]
  15. Absence of DNA polymerase theta results in decreased somatic hypermutation frequency and altered mutation patterns in Ig genes. Masuda, K., Ouchida, R., Hikida, M., Nakayama, M., Ohara, O., Kurosaki, T., O-Wang, J. DNA Repair (Amst.) (2006) [Pubmed]
  16. Multiple PolK (POLK) transcripts in mammalian testis. Guo, C., Gao, T., Confer, N., Velasco-Miguel, S., Friedberg, E.C. DNA Repair (Amst.) (2005) [Pubmed]
  17. Absorption, disposition and metabolism of di-isononyl phthalate (DINP) in F-344 rats. McKee, R.H., El-Hawari, M., Stoltz, M., Pallas, F., Lington, A.W. Journal of applied toxicology : JAT. (2002) [Pubmed]
  18. The promoter of the human sodium/iodide symporter responds to certain phthalate plasticisers. Breous, E., Wenzel, A., Loos, U. Mol. Cell. Endocrinol. (2005) [Pubmed]
  19. The role of inhibition of gap junctional intercellular communication in rodent liver tumor induction by phthalates: review of data on selected phthalates and the potential relevance to man. McKee, R.H. Regulatory toxicology and pharmacology : RTP. (2000) [Pubmed]
  20. University of Louisville experience and contributions to pediatric trauma care. Bond, S., Fallat, M.E. Am. J. Surg. (2005) [Pubmed]
  21. Current treatment of intraabdominal infections. Chong, A.J., Dellinger, E.P. Surgical technology international. (2005) [Pubmed]
 
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