Somatic mutation hotspots correlate with DNA polymerase eta error spectrum.
Mutational spectra analysis of 15 immunoglobulin genes suggested that consensus motifs RGYW and WA were universal descriptors of somatic hypermutation. Highly mutable sites, "hotspots", that matched WA were preferentially found in one DNA strand and RGYW hotspots were found in both strands. Analysis of base-substitution hotspots in DNA polymerase error spectra showed that 33 of 36 hotspots in the human polymerase eta spectrum conformed to the WA consensus. This and four other characteristics of polymerase eta substitution specificity suggest that errors introduced by this enzyme during synthesis of the nontranscribed DNA strand in variable regions may contribute to strand-specific somatic hypermutagenesis of immunoglobulin genes at A-T base pairs.
Rogozin
I B
IB
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
Pavlov
Y I
YI
Bebenek
K
K
Matsuda
T
T
Kunkel
T A
TA
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D016384:Consensus Sequence; D004247:DNA / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D005803:Genes, Immunoglobulin; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D000099270:Y-Family DNA Polymerases
D004247:DNA; D004259:DNA-Directed DNA Polymerase; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases