Azacitidine is a ribonucleoside, so it is incorporated into RNA to a larger extent than into DNA. In contrast, decitabine (5-aza-2-deoxycytidine) is a deoxyribonucleoside, so it can only incorporate into DNA. Azacitidines incorporation into RNA leads to the disassembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of proteins. Its incorporation into DNA leads to covalent binding with DNA methyltransferases, which prevents DNA synthesis and subsequently leads to cytotoxicity. It has been shown effective against human immunodeficiency virus in vitro and human T-lymphotropic virus. Inhibition of methylation
After azanucleosides such as azacitidine have been metabolized to 5-aza-2′-deoxycytidine-triphosphate (aka, decitabine-triphosphate), they can be incorporated into DNA and azacytosine can be substituted for cytosine. Azacytosine-guanine dinucleotides are recognized as substrate by the DNA methyltransferases, which catalyze the methylation reaction by a nucleophilic attack. This results in a covalent bond between the carbon-6 atom of the cytosine ring and the enzyme. The bond is normally resolved by beta-elimination through the carbon-5 atom, but this latter reaction does not occur with azacytosine because its carbon-5 is substituted by nitrogen, leaving the enzyme covalently bound to DNA and blocking its DNA methyltransferase function. In addition, the covalent protein adduction also compromises the functionality of DNA and triggers DNA damage signaling, resulting in the degradation of trapped DNA methyltransferases. As a consequence, methylation marks become lost during DNA replication.
Dysmelia (from the Greek dys (δυσ-), "bad" + mélos (μέλος), "limb" + English suffix -ia) is a congenital disorder of a limb resulting from a disturbance in embryonic development. Types
Dysmelia can refer to
missing (aplasia) limbs: amelia, oligodactyly, congenital amputation e.g. tibial or radial aplasia
malformation of limbs: shortening (micromelia, rhizomelia or mesomelia), ectrodactyly, phocomelia, meromelia, syndactyly, brachydactyly, club foot
too many limbs: polymelia, polydactyly, polysyndactyly
others: tetraamelia, hemimelia, symbrachydactyly

Occurrence rate
Birth defects involving limbs occur in 1 per 1000. Causes
Dysmelia can be caused by
Inheritance of abnormal genes, e.g. polydactyly, ectrodactyly or brachydactyly, symptoms of deformed limbs then often occur in combination with other symptoms (syndromes)
external causes during pregnancy (thus not inherited), e.g. via amniotic band syndrome
teratogenic drugs (e.g. thalidomide, which causes phocomelia) or environmental chemicals
ionizing radiation (nuclear weapons, radioiodine, radiation therapy)
infections
metabolic imbalance

Syndromes with dysmelia
References
External links
DysNet: An organisation for people affected by Dysmelia (congenital limb difference)
Reach: Association for Children with Upper Limb Deficiency)