Cytidine deaminase explained

Cytidine deaminase is an enzyme that in humans is encoded by the CDA gene.^{[1] [2] [3]}

This gene encodes an enzyme involved in pyrimidine salvaging. The encoded protein forms a homotetramer that catalyzes the irreversible hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively. It is one of several deaminases responsible for maintaining the cellular pyrimidine pool. Mutations in this gene are associated with decreased sensitivity to the cytosine nucleoside analogue cytosine arabinoside used in the treatment of certain childhood leukemias.^[3] Most cytidine deaminases act on RNA, and the few that act on DNA require ssDNA.^[4]

A related activation-induced (cytidine) deaminase (AID) regulates antibody diversification, especially the process of somatic hypermutation.

Further reading

• Wentworth DF, Wolfenden R . On the interaction of 3,4,5,6-tetrahydrouridine with human liver cytidine deaminase . Biochemistry . 14 . 23 . 5099–105 . November 1975 . 53069 . 10.1021/bi00694a012 .
• Laliberté J, Momparler RL . Human cytidine deaminase: purification of enzyme, cloning, and expression of its complementary DNA . Cancer Research . 54 . 20 . 5401–7 . October 1994 . 7923172 .
• Saccone S, Besati C, Andreozzi L, Della Valle G, Garattini E, Terao M . Assignment of the human cytidine deaminase (CDA) gene to chromosome 1 band p35-p36.2 . Genomics . 22 . 3 . 661–2 . August 1994 . 8001985 . 10.1006/geno.1994.1448 .
• Gran C, Bøyum A, Johansen RF, Løvhaug D, Seeberg EC . Growth inhibition of granulocyte-macrophage colony-forming cells by human cytidine deaminase requires the catalytic function of the protein . Blood . 91 . 11 . 4127–35 . June 1998 . 10.1182/blood.V91.11.4127 . 9596658 .
• Somasekaram A, Jarmuz A, How A, Scott J, Navaratnam N . Intracellular localization of human cytidine deaminase. Identification of a functional nuclear localization signal . The Journal of Biological Chemistry . 274 . 40 . 28405–12 . October 1999 . 10497201 . 10.1074/jbc.274.40.28405 . free .
• Wistow G, Bernstein SL, Wyatt MK, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K . 6 . Expressed sequence tag analysis of adult human lens for the NEIBank Project: over 2000 non-redundant transcripts, novel genes and splice variants . Molecular Vision . 8 . 171–84 . June 2002 . 12107413 .
• Taysi S, Polat MF, Sari RA, Bakan E . Serum adenosine deaminase and cytidine deaminase activities in patients with systemic lupus erythematosus . Clinical Chemistry and Laboratory Medicine . 40 . 5 . 493–5 . May 2002 . 12113294 . 10.1515/CCLM.2002.085 . 32965037 .
• Bransteitter R, Pham P, Scharff MD, Goodman MF . Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase . Proceedings of the National Academy of Sciences of the United States of America . 100 . 7 . 4102–7 . April 2003 . 12651944 . 153055 . 10.1073/pnas.0730835100 . 2003PNAS..100.4102B . free .
• Sun ZQ, Jiang B, Zhao XS, Bao L, Wu T, Lu XJ, Kong Y, Wang DB . 6 . [Expression of cytidine deaminase mRNA in bone marrow cells from patients with acute leukemia] . Zhongguo Shi Yan Xue Ye Xue Za Zhi . 11 . 3 . 246–50 . June 2003 . 12844405 .
• Vincenzetti S, Costanzi S, Cristalli G, Mariani P, Quadrini B, Cammertoni N, Vita A . Intersubunit interactions in human cytidine deaminase . Nucleosides, Nucleotides & Nucleic Acids . 22 . 5–8 . 1535–8 . 2003 . 14565460 . 10.1081/NCN-120023028 . 8626156 .
• Costanzi S, Vincenzetti S, Vita A, Lambertucci C, Taffi S, Volpini R, Vittori S, Cristalli G . 6 . Human cytidine deaminase: understanding the catalytic mechanism . Nucleosides, Nucleotides & Nucleic Acids . 22 . 5–8 . 1539–43 . 2003 . 14565461 . 10.1081/NCN-120023029 . 6849333 .
• Ge Y, Jensen TL, Stout ML, Flatley RM, Grohar PJ, Ravindranath Y, Matherly LH, Taub JW . 6 . The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines . Cancer Research . 64 . 2 . 728–35 . January 2004 . 14744791 . 10.1158/0008-5472.CAN-03-2456 . free .
• Vincenzetti S, De Sanctis G, Costanzi S, Cristalli G, Mariani P, Mei G, Neuhard J, Natalini P, Polzonetti V, Vita A . 6 . Functional properties of subunit interactions in human cytidine deaminase . Protein Engineering . 16 . 12 . 1055–61 . December 2003 . 14983087 . 10.1093/protein/gzg117 . free .
• 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, Morrin 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 . 6 . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Research . 14 . 10B . 2121–7 . October 2004 . 15489334 . 528928 . 10.1101/gr.2596504 .
• Chung SJ, Fromme JC, Verdine GL . Structure of human cytidine deaminase bound to a potent inhibitor . Journal of Medicinal Chemistry . 48 . 3 . 658–60 . February 2005 . 15689149 . 10.1021/jm0496279 .
• Vincenzetti S, Mariani PL, Cammertoni N, Polzonetti V, Natalini P, Quadrini B, Volpini R, Vita A . 6 . Isoenzymatic forms of human cytidine deaminase . Protein Engineering, Design & Selection . 17 . 12 . 871–7 . December 2004 . 15713780 . 10.1093/protein/gzh101 . free .
• Costanzi S, Vincenzetti S, Cristalli G, Vita A . Human cytidine deaminase: a three-dimensional homology model of a tetrameric metallo-enzyme inferred from the crystal structure of a distantly related dimeric homologue . Journal of Molecular Graphics & Modelling . 25 . 1 . 10–6 . September 2006 . 16303324 . 10.1016/j.jmgm.2005.10.008 .

Notes and References

1. Kühn K, Bertling WM, Emmrich F . Cloning of a functional cDNA for human cytidine deaminase (CDD) and its use as a marker of monocyte/macrophage differentiation . Biochemical and Biophysical Research Communications . 190 . 1 . 1–7 . January 1993 . 8422236 . 10.1006/bbrc.1993.1001 .
2. Demontis S, Terao M, Brivio M, Zanotta S, Bruschi M, Garattini E . Isolation and characterization of the gene coding for human cytidine deaminase . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1443 . 3 . 323–33 . December 1998 . 9878810 . 10.1016/s0167-4781(98)00235-8 .
3. Web site: Entrez Gene: CDA cytidine deaminase.
4. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR . Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage . Nature . 533 . 7603 . 420–4 . May 2016 . 27096365 . 4873371 . 10.1038/nature17946 . 2016Natur.533..420K .