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Review
. 2009 Mar 12;364(1517):563-8.
doi: 10.1098/rstb.2008.0186.

Uracil in DNA and its processing by different DNA glycosylases

Torkild Visnes  1 , Berit Doseth, Henrik Sahlin Pettersen, Lars Hagen, Mirta M L Sousa, Mansour Akbari, Marit Otterlei, Bodil Kavli, Geir Slupphaug, Hans E Krokan
Affiliations
Review

Uracil in DNA and its processing by different DNA glycosylases

Torkild Visnes et al. Philos Trans R Soc Lond B Biol Sci. .

Abstract

Uracil in DNA may result from incorporation of dUMP during replication and from spontaneous or enzymatic deamination of cytosine, resulting in U:A pairs or U:G mismatches, respectively. Uracil generated by activation-induced cytosine deaminase (AID) in B cells is a normal intermediate in adaptive immunity. Five mammalian uracil-DNA glycosylases have been identified; these are mitochondrial UNG1 and nuclear UNG2, both encoded by the UNG gene, and the nuclear proteins SMUG1, TDG and MBD4. Nuclear UNG2 is apparently the sole contributor to the post-replicative repair of U:A lesions and to the removal of uracil from U:G contexts in immunoglobulin genes as part of somatic hypermutation and class-switch recombination processes in adaptive immunity. All uracil-DNA glycosylases apparently contribute to U:G repair in other cells, but they are likely to have different relative significance in proliferating and non-proliferating cells, and in different phases of the cell cycle. There are also some indications that there may be species differences in the function of the uracil-DNA glycosylases.

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Figures

Figure 1
Figure 1
Model of B-cell lymphoma development in Ung-deficient mice. (a) The pathway illustrates the normal development of Ung+/+ B cells after translocation to secondary lymphoid tissues, leading to antibody-secreting plasma cells and memory cells. (b) The pathway models how cytokine dysregulation and increased accumulation of untargeted mutations in Ung−/− B cells result in lymphoid hyperplasia and increased number of cells having a mutator phenotype. Eventually, this may lead to the development of follicular lymphoma and progression to diffuse large B-cell lymphoma.
Figure 2
Figure 2
Model showing sources for the generation of uracil in DNA and the repair pathways of the lesions (a) in non-replicating chromatin and (b) at the replication fork. Uracil excision by UNG2 in single-stranded DNA (ssDNA) at the replication fork will probably result in stalled replication that will initiate recombination or translesion synthesis (TLS). The uracil-initiated diversification pathways in activated B cells are highlighted in red, newly replicated DNA is in blue and RNA is in green. U, uracil; HmU, hydroxymethyluracil.
See this image and copyright information in PMC

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