Biology:PNKP
From HandWiki
Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Bifunctional polynucleotide phosphatase/kinase is an enzyme that in humans is encoded by the PNKP gene.[1][2][3] A detailed structural study of the crystallized mouse protein examined both the 5´-polynucleotide kinase and 3’-polynucleotide phosphatase activities.[4] Additional features of the peptide sequence include a forkhead association (FHA) domain, ATP binding site and nuclear and mitochondrial localization sequences.
Interactions
PNKP has been shown to interact with DNA polymerase beta[5] and XRCC1.[5][6]
Role in neurologic disease
The human gene encoding PNKP was observed to be mutated in patients[7][8][9][10] with microcephaly, seizures and defects in DNA repair. A type of recessive ataxia is also associated with PNKP mutations.[11] There are also newly characterized pathological variants of PNKP.[12] Model organisms such as mice and Drosophila have been used to generate further insights.[13][14]
References
- ↑ "Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3'-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage". J. Biol. Chem. 274 (34): 24176–86. September 1999. doi:10.1074/jbc.274.34.24176. PMID 10446192.
- ↑ "Molecular characterization of a human DNA kinase". J. Biol. Chem. 274 (34): 24187–94. September 1999. doi:10.1074/jbc.274.34.24187. PMID 10446193.
- ↑ "Entrez Gene: PNKP polynucleotide kinase 3'-phosphatase". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11284.
- ↑ Garces, Fernando; Pearl, Laurence H.; Oliver, Antony W. (November 2011). "The Structural Basis for Substrate Recognition by Mammalian Polynucleotide Kinase 3′ Phosphatase" (in en). Molecular Cell 44 (3): 385–396. doi:10.1016/j.molcel.2011.08.036. PMID 22055185.
- ↑ 5.0 5.1 "XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair". Cell 104 (1): 107–17. January 2001. doi:10.1016/S0092-8674(01)00195-7. PMID 11163244.
- ↑ "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. 2007. doi:10.1038/msb4100134. PMID 17353931.
- ↑ Dumitrache, Lavinia C.; McKinnon, Peter J. (2017). "Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease" (in en). Mechanisms of Ageing and Development 161 (Pt A): 121–129. doi:10.1016/j.mad.2016.04.009. PMID 27125728.
- ↑ Shen, Jun; Gilmore, Edward C; Marshall, Christine A; Haddadin, Mary; Reynolds, John J; Eyaid, Wafaa; Bodell, Adria; Barry, Brenda et al. (2010). "Mutations in PNKP cause microcephaly, seizures and defects in DNA repair" (in en). Nat Genet 42 (3): 245–249. doi:10.1038/ng.526. ISSN 1061-4036. PMID 20118933.
- ↑ Issa, Lina; Mueller, Katrin; Seufert, Katja; Kraemer, Nadine; Rosenkotter, Henning; Ninnemann, Olaf; Buob, Michael; Kaindl, Angela M et al. (2013). "Clinical and cellular features in patients with primary autosomal recessive microcephaly and a novel CDK5RAP2 mutation" (in en). Orphanet Journal of Rare Diseases 8 (1): 59. doi:10.1186/1750-1172-8-59. ISSN 1750-1172. PMID 23587236.
- ↑ Kalasova, Ilona; Hanzlikova, Hana; Gupta, Neerja; Li, Yun; Altmüller, Janine; Reynolds, John J.; Stewart, Grant S.; Wollnik, Bernd et al. (2019). "Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ" (in en). Neurol Genet 5 (2): e320. doi:10.1212/NXG.0000000000000320. ISSN 2376-7839. PMID 31041400.
- ↑ Bras, Jose; Alonso, Isabel; Barbot, Clara; Costa, Maria Manuela; Darwent, Lee; Orme, Tatiana; Sequeiros, Jorge; Hardy, John et al. (2015). "Mutations in PNKP Cause Recessive Ataxia with Oculomotor Apraxia Type 4" (in en). The American Journal of Human Genetics 96 (3): 474–479. doi:10.1016/j.ajhg.2015.01.005. PMID 25728773.
- ↑ Gatti, Marta; Magri, Stefania; Nanetti, Lorenzo; Sarto, Elisa; Di Bella, Daniela; Salsano, Ettore; Pantaleoni, Chiara; Mariotti, Caterina et al. (2019). "From congenital microcephaly to adult onset cerebellar ataxia: Distinct and overlapping phenotypes in patients with PNKP gene mutations" (in en). American Journal of Medical Genetics Part A 179 (11): 2277–2283. doi:10.1002/ajmg.a.61339. ISSN 1552-4825. PMID 31436889.
- ↑ Shimada, Mikio; Dumitrache, Lavinia C; Russell, Helen R; McKinnon, Peter J (2015). "Polynucleotide kinase–phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability" (in en). The EMBO Journal 34 (19): 2465–2480. doi:10.15252/embj.201591363. ISSN 0261-4189. PMID 26290337.
- ↑ Chakraborty, Anirban; Tapryal, Nisha; Venkova, Tatiana; Mitra, Joy; Vasquez, Velmarini; Sarker, Altaf H.; Duarte-Silva, Sara; Huai, Weihan et al. (2020-04-07). "Deficiency in classical nonhomologous end-joining–mediated repair of transcribed genes is linked to SCA3 pathogenesis" (in en). Proceedings of the National Academy of Sciences 117 (14): 8154–8165. doi:10.1073/pnas.1917280117. ISSN 0027-8424. PMID 32205441. Bibcode: 2020PNAS..117.8154C.
Further reading
- "XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair". Cell 104 (1): 107–17. 2001. doi:10.1016/S0092-8674(01)00195-7. PMID 11163244.
- "Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining". EMBO J. 21 (11): 2827–32. 2002. doi:10.1093/emboj/21.11.2827. PMID 12032095.
- "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. 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Spectroscopic studies of DNA and ATP binding to human polynucleotide kinase: evidence for a ternary complex". Biochemistry 42 (41): 12077–84. 2003. doi:10.1021/bi030127b. PMID 14556639.
- "The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks". Cell 117 (1): 17–28. 2004. doi:10.1016/S0092-8674(04)00206-5. PMID 15066279.
- "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. 2004. doi:10.1101/gr.2334104. PMID 15231748.
- "AP endonuclease-independent DNA base excision repair in human cells". Mol. Cell 15 (2): 209–20. 2004. doi:10.1016/j.molcel.2004.06.003. PMID 15260972.
- "Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV". EMBO J. 23 (19): 3874–85. 2004. doi:10.1038/sj.emboj.7600375. PMID 15385968.
- "Nucleolar proteome dynamics". Nature 433 (7021): 77–83. 2005. doi:10.1038/nature03207. PMID 15635413. Bibcode: 2005Natur.433...77A.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "Involvement of polynucleotide kinase in a poly(ADP-ribose) polymerase-1-dependent DNA double-strand breaks rejoining pathway". J. Mol. Biol. 356 (2): 257–65. 2006. doi:10.1016/j.jmb.2005.11.028. PMID 16364363.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. 2007. doi:10.1038/msb4100134. PMID 17353931.
- "Human polynucleotide kinase participates in repair of DNA double-strand breaks by nonhomologous end joining but not homologous recombination". Cancer Res. 67 (14): 6619–25. 2007. doi:10.1158/0008-5472.CAN-07-0480. PMID 17638872.
- "XRCC1 stimulates polynucleotide kinase by enhancing its damage discrimination and displacement from DNA repair intermediates". J. Biol. Chem. 282 (38): 28004–13. 2007. doi:10.1074/jbc.M704867200. PMID 17650498.
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