| First Author | Sharbeen G | Year | 2012 |
| Journal | J Exp Med | Volume | 209 |
| Issue | 5 | Pages | 965-74 |
| PubMed ID | 22529268 | Mgi Jnum | J:185140 |
| Mgi Id | MGI:5427525 | Doi | 10.1084/jem.20112379 |
| Citation | Sharbeen G, et al. (2012) Ectopic restriction of DNA repair reveals that UNG2 excises AID-induced uracils predominantly or exclusively during G1 phase. J Exp Med 209(5):965-74 |
| abstractText | Immunoglobulin (Ig) affinity maturation requires the enzyme AID, which converts cytosines (C) in Ig genes into uracils (U). This alone produces C:G to T:A transition mutations. Processing of U:G base pairs via U N-glycosylase 2 (UNG2) or MutSalpha generates further point mutations, predominantly at G:C or A:T base pairs, respectively, but it is unclear why processing is mutagenic. We aimed to test whether the cell cycle phase of U processing determines fidelity. Accordingly, we ectopically restricted UNG2 activity in vivo to predefined cell cycle phases by fusing a UNG2 inhibitor peptide to cell cycle-regulated degradation motifs. We found that excision of AID-induced U by UNG2 occurs predominantly during G1 phase, inducing faithful repair, mutagenic processing, and class switching. Surprisingly, UNG2 does not appear to process U:G base pairs at all in Ig genes outside G1 phase. |
