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Two levels of protection for the B cell genome during somatic hypermutation |
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Notes for this articleThe authors of this paper sequenced ~1kb in the 1.5kb regions downstream of the TSS for 118 genes in WT mouse B cells, and 31 genes in AID-/- mouse B cells. The genes from WT B cells were always more frequently mutated than the same genes in AID-/-. However, some genes were more mutated than others, indicating that AID does not act at the same level everywhere in the genome.
In the most frequently mutated genes, mutations were seemingly highly biased towards the somatic hypermutation hotspot sequence RGYW/WRCY. They also exhibited a significant A greater than T mutation bias on the non-transcribed strand (why exactly is not clear to me).
Because MutS and Ung are involved in both high-fidelity and error-prone repair, the authors sequenced genes from B cells in MutS-/- Ung-/- mice. They found genes with a very large mutant over WT GC->AT mutation ratios (indicating that high-fidelity DNA repair is acting in WT), and lower (~1) ratios (indicating that no high fidelity repair in going on). That suggests that some genes undergo a lot of AID-induced damage, but that this damage is fixed (but not always) by the MutS or Ung machinery.
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