Effects of sequence and structure on the hypermutability of immunoglobulin genes

被引：67

作者：

Michael, N

Martin, TE

Nicolae, D

Kim, N

Padjen, K

Zhan, P

Nguyen, H

Pinkert, C

Storb, U ^{[1
]}

机构：

[1] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA

[2] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA

[3] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA

[4] Univ Chicago, Dept Stat, Chicago, IL 60637 USA

[5] Univ Rochester, Dept Pathol & Lab Med, Rochester, NY 14642 USA

来源：

IMMUNITY | 2002年 / 16卷 / 01期

关键词：

D O I：

10.1016/S1074-7613(02)00261-3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Somatic hypermutation (SHM) is investigated in related immunoglobulin transgenes that differ in a short artificial sequence designed to vary the content of hotspot motifs and the potential to form RNA or DNA secondary structures. Mutability depends on hotspots, not secondary structure. Hotspot motifs predict about 50% of the mutations; the rest are in neutral and coldspots. Clusters of mutations and the sequential addition of mutations found in cell pedigrees suggest epigenetic attributes of SHM. Sometime in SHM, an essential factor seems to become limiting. Particular error-prone DNA polymerases appear to create mutations in hotspots on the top and bottom DNA strands throughout the target and the SHM process. One transgene is superhypermutable in all regions, suggesting the presence of a cis-element that enhances SHM.

引用

页码：123 / 134

页数：12

共 45 条

[1] Critical test of hot spot motifs for immunoglobulin hypermutation [J].