title: The pattern of somatic hypermutation of Ig genes is altered when p53 is inactivated.
abstract: Mice with a deletion of the p53 gene have normal antibody titers against sheep red blood cells and normal switching to all Ig isotypes. In older mice (11 and 16 weeks old) the somatic hypermutation (SHM) frequencies are progressively reduced. In young mice (8 weeks old) with p53 deletion, the SHM frequencies are normal. However, the mutation pattern is changed in all p53-/- mice: mutations at A are increased. Surprisingly, deletion of the Ung2 gene in addition to the deletion of p53 corrected the A mutation frequencies to those of control mice. Known interactions of p53 protein with several proteins involved in error-prone BER during SHM may explain these findings. There is no indication that the absence of p53 affects the function of AID. Inactivation of p21 does not alter SHM, supporting the idea that the p53 protein is involved in SHM by its direct association with the SHM process. There is no significant change of mutations at T. Thus, the hypermutability at A is strand-biased (transcription? replication?). The translesion polymerase pol eta has so far been found to be the sole mutator at A and T in mice. However, the pattern in p53-/- mice is compatible with the possible inhibition by p53 of another translesion polymerase, pol iota, which in the absence of p53 may be recruited to error-prone repair of abasic sites in SHM.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, United States.
authors.forename: Sarayu
authors.initials: S
authors.lastname: Ratnam
authors.forename: Grazyna
authors.initials: G
authors.lastname: Bozek
authors.forename: Dan
authors.initials: D
authors.lastname: Nicolae
authors.forename: Ursula
authors.initials: U
authors.lastname: Storb
mesh_terms: D000818:Animals; D053843:DNA Mismatch Repair; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027041:Somatic Hypermutation, Immunoglobulin; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53