In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 109.8-109.8
Abstract:
Immunoglobulin (Ig) affinity maturation requires the enzyme AID, which converts cytosines in Ig genes into uracils. This alone produces C:G to A:T transition mutations. Processing of U:G base pairs via UNG2 or MutSα generates further point mutations, predominantly at G:C or A:T base pairs, respectively, but it is unknown why processing is mutagenic. We aimed to test whether the cell cycle phase of uracil processing determines fidelity. Accordingly, we ectopically restricted UNG2 activity in vivo to pre-defined cell cycle phases by fusing a transduced inhibitor peptide to cell cycle regulated degradation motifs. We conclude that excision of AID-induced uracils by UNG2 occurs exclusively in G1-phase, leading to mutation alongside predominantly correct repair. Surprisingly, UNG2 does not seem to process U:G base pairs at all in Ig genes undergoing replication. Preliminary data indicates that processing of AID-induced uracils via MutSα is also cell cycle regulated.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.188.Supp.109.8
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
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