DNA-uracil and human pathology. Export

@article{citeulike:5836544, abstract = {Uracil is usually an inappropriate base in DNA, but it is also a normal intermediate during somatic hypermutation (SHM) and class switch recombination (CSR) in adaptive immunity. In addition, uracil is introduced into retroviral DNA by the host as part of a defence mechanism. The sources of uracil in DNA are spontaneous or enzymatic deamination of cytosine (U:G mispairs) and incorporation of dUTP (U:A pairs). Uracil in DNA is removed by a uracil-DNA glycosylase. The major ones are nuclear UNG2 and mitochondrial UNG1 encoded by the UNG-gene, and SMUG1 that also removes oxidized pyrimidines, e.g. 5-hydroxymethyluracil. The other ones are TDG that removes U and T from mismatches, and MBD4 that removes U from CpG contexts. UNG2 is found in replication foci during the S-phase and has a distinct role in repair of U:A pairs, but it is also important in U:G repair, a function shared with SMUG1. SHM is initiated by activation-induced cytosine deaminase (AID), followed by removal of U by UNG2. Humans lacking UNG2 suffer from recurrent infections and lymphoid hyperplasia, and have skewed SHM and defective CSR, resulting in elevated IgM and strongly reduced IgG, IgA and IgE. UNG-defective mice also develop B-cell lymphoma late in life. In the defence against retrovirus, e.g. HIV-1, high concentrations of dUTP in the target cells promotes misincorporation of dUMP-, and host cell APOBEC proteins may promote deamination of cytosine in the viral DNA. This facilitates degradation of viral DNA by UNG2 and AP-endonuclease. However, viral proteins Vif and Vpr counteract this defense by mechanisms that are now being revealed. In conclusion, uracil in DNA is both a mutagenic burden and a tool to modify DNA for diversity or degradation.}, author = {Sousa, Mirta M. and Krokan, Hans E. and Slupphaug, Geir}, citeulike-article-id = {5836544}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.mam.2007.04.006}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17590428}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17590428}, doi = {10.1016/j.mam.2007.04.006}, issn = {0098-2997}, journal = {Molecular aspects of medicine}, keywords = {damage, dna, review, ung}, number = {3-4}, pages = {276--306}, posted-at = {2009-09-24 21:50:58}, priority = {2}, title = {DNA-uracil and human pathology.}, url = {http://dx.doi.org/10.1016/j.mam.2007.04.006}, volume = {28}, year = {2007} }

TY - JOUR ID - citeulike:5836544 L3 - citeulike-article-id:5836544 N2 - Uracil is usually an inappropriate base in DNA, but it is also a normal intermediate during somatic hypermutation (SHM) and class switch recombination (CSR) in adaptive immunity. In addition, uracil is introduced into retroviral DNA by the host as part of a defence mechanism. The sources of uracil in DNA are spontaneous or enzymatic deamination of cytosine (U:G mispairs) and incorporation of dUTP (U:A pairs). Uracil in DNA is removed by a uracil-DNA glycosylase. The major ones are nuclear UNG2 and mitochondrial UNG1 encoded by the UNG-gene, and SMUG1 that also removes oxidized pyrimidines, e.g. 5-hydroxymethyluracil. The other ones are TDG that removes U and T from mismatches, and MBD4 that removes U from CpG contexts. UNG2 is found in replication foci during the S-phase and has a distinct role in repair of U:A pairs, but it is also important in U:G repair, a function shared with SMUG1. SHM is initiated by activation-induced cytosine deaminase (AID), followed by removal of U by UNG2. Humans lacking UNG2 suffer from recurrent infections and lymphoid hyperplasia, and have skewed SHM and defective CSR, resulting in elevated IgM and strongly reduced IgG, IgA and IgE. UNG-defective mice also develop B-cell lymphoma late in life. In the defence against retrovirus, e.g. HIV-1, high concentrations of dUTP in the target cells promotes misincorporation of dUMP-, and host cell APOBEC proteins may promote deamination of cytosine in the viral DNA. This facilitates degradation of viral DNA by UNG2 and AP-endonuclease. However, viral proteins Vif and Vpr counteract this defense by mechanisms that are now being revealed. In conclusion, uracil in DNA is both a mutagenic burden and a tool to modify DNA for diversity or degradation. IS - 3-4 JF - Molecular aspects of medicine SN - 0098-2997 EP - 306 TI - DNA-uracil and human pathology. VL - 28 SP - 276 KW - damage KW - dna KW - review KW - ung AU - Sousa, Mirta AU - Krokan, Hans AU - Slupphaug, Geir PY - 2007///g UR - http://dx.doi.org/10.1016/j.mam.2007.04.006 ER -