Abstract:
:Hypermutation in immunoglobulin genes produces a high frequency of substitutions of all four bases, which are likely generated by low-fidelity DNA polymerases. Indeed, humans deficient for DNA polymerase (pol) eta have decreased substitutions of A.T base pairs in variable and switch regions. To study the role of pol eta in a genetically tractable system, we created mice lacking pol eta. B cells from Polh-/- mice produced normal amounts of IgG, indicating that pol eta does not affect class switch recombination. Similar to their human counterparts, variable and switch regions from Polh-/- mice had fewer substitutions of A.T base pairs and correspondingly more mutations of C.G base pairs, which firmly establishes a central role for pol eta in hypermutation. Notably, the location and types of substitutions differ markedly from those in Msh6-/- clones, which also have fewer A.T mutations. The data suggest that pol eta preferentially synthesizes a repair patch on the nontranscribed strand, whereas MSH6 functions to generate the patch.
journal_name
Proc Natl Acad Sci U S Aauthors
Martomo SA,Yang WW,Wersto RP,Ohkumo T,Kondo Y,Yokoi M,Masutani C,Hanaoka F,Gearhart PJdoi
10.1073/pnas.0501852102keywords:
subject
Has Abstractpub_date
2005-06-14 00:00:00pages
8656-61issue
24eissn
0027-8424issn
1091-6490pii
0501852102journal_volume
102pub_type
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