In:
The Journal of Experimental Medicine, Rockefeller University Press, Vol. 204, No. 8 ( 2007-08-06), p. 1989-1998
Abstract:
B cells use translesion DNA synthesis (TLS) to introduce somatic mutations around genetic lesions caused by activation-induced cytidine deaminase. Monoubiquitination at lysine164 of proliferating cell nuclear antigen (PCNAK164) stimulates TLS. To determine the role of PCNAK164 modifications in somatic hypermutation, PCNAK164R knock-in mice were generated. PCNAK164R/K164R mutants are born at a sub-Mendelian frequency. Although PCNAK164R/K164R B cells proliferate and class switch normally, the mutation spectrum of hypermutated immunoglobulin (Ig) genes alters dramatically. A strong reduction of mutations at template A/T is associated with a compensatory increase at G/C, which is a phenotype similar to polymerase η (Polη) and mismatch repair–deficient B cells. Mismatch recognition, monoubiquitinated PCNA, and Polη likely cooperate in establishing mutations at template A/T during replication of Ig genes.
Type of Medium:
Online Resource
ISSN:
1540-9538
,
0022-1007
DOI:
10.1084/jem.20070902
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2007
detail.hit.zdb_id:
1477240-1
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