[Uracil in DNA--friend or foe?].
Uracil may arise in DNA, in small quantities as a result of spontaneous cytosine deamination or/and misincorporation of dUMP during DNA replication. However, just recently uracil formation via enzymatic deamiantion of cytosine, has been found to underlies diversification of Ig genes and inhibition of retroviral infection. DNA deamination is the only known programme in mammalian development in which the coding capacity of the genome is changed by targeted modification of deoxycitidine. In this paper we will review: i/sources of the origin of uracil in DNA, ii/the function of activation induced cytidine deaminase (AID) the enzyme which is responsible for cytidine deamination in Ig genes of B cell clones iii/some properties of the enzymes responsible for the excision of uracil. The role of uracil and above mentioned enzymes in Ig diversification process, which comprises somatic hypermutation and class switch recombination will also be discussed. Finally, we will discuss possible involvement of aberrantly expressed AID and presence of uracil in DNA, in carcinogenesis.
Oliński
Ryszard
R
Katedra i Zakład Biochemii Klinicznej Collegium Medicum im. L. Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu, Bydgoszcz. ryszardo@cm.umk.pl
Jurgowiak
Marek
M
D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D012192:Retroviridae Infections / Q000235:genetics / Q000517:prevention & control; D027041:Somatic Hypermutation, Immunoglobulin; D014498:Uracil / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D003856:Deoxyuracil Nucleotides; D014498:Uracil; D004247:DNA; C007267:2'-deoxyuridylic acid; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase