II. Correlations between secondary structure stability and mutation frequency during somatic hypermutation

Barbara E. Wright; Karen H. Schmidt; Nick Davis; Aaron T. Hunt; Michael F. Minnick

doi:10.1016/j.molimm.2008.05.012

II. Correlations between secondary structure stability and mutation frequency during somatic hypermutation

Barbara E. Wright, Karen H. Schmidt, Nick Davis, Aaron T. Hunt, Michael F. Minnick

Division of Biological and Biomedical Sciences

University of Montana

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

The role of secondary structures and base mutability at different levels of transcription and supercoiling is analyzed in variable region antibody genes VH5, VH94 and VH186.2. The data are consistent with a model of somatic hypermutation in which increasing levels of transcription and secondary structure stability correlate with the initial formation of successive mutable sites. Encoded differences exist in stem length and the number of GC pairs at low versus high levels of transcription in CDRs. These circumstances simplify the complexities of coordinating mutagenesis by confining this process to each mutable site successively, as they form in response to increasing levels of transcription during affinity maturation.

Original language	English
Pages (from-to)	3600-3608
Number of pages	9
Journal	Molecular Immunology
Volume	45
Issue number	13
DOIs	https://doi.org/10.1016/j.molimm.2008.05.012
State	Published - Aug 2008

Funding

This research was funded by NIH grant R01CA099242 and the Stella Duncan Memorial Research Institute.

Funder number
R01CA099242

Keywords

Computer model
DNA secondary structures
Somatic hypermutation
Transcription
VH genes

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10.1016/j.molimm.2008.05.012

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title = "II. Correlations between secondary structure stability and mutation frequency during somatic hypermutation",

abstract = "The role of secondary structures and base mutability at different levels of transcription and supercoiling is analyzed in variable region antibody genes VH5, VH94 and VH186.2. The data are consistent with a model of somatic hypermutation in which increasing levels of transcription and secondary structure stability correlate with the initial formation of successive mutable sites. Encoded differences exist in stem length and the number of GC pairs at low versus high levels of transcription in CDRs. These circumstances simplify the complexities of coordinating mutagenesis by confining this process to each mutable site successively, as they form in response to increasing levels of transcription during affinity maturation.",

keywords = "Computer model, DNA secondary structures, Somatic hypermutation, Transcription, VH genes",

author = "Wright, \{Barbara E.\} and Schmidt, \{Karen H.\} and Nick Davis and Hunt, \{Aaron T.\} and Minnick, \{Michael F.\}",

note = "Funding Information: This research was funded by NIH grant R01CA099242 and the Stella Duncan Memorial Research Institute.",

year = "2008",

month = aug,

doi = "10.1016/j.molimm.2008.05.012",

language = "English",

volume = "45",

pages = "3600--3608",

journal = "Molecular Immunology",

issn = "0161-5890",

publisher = "Elsevier Ltd",

number = "13",

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TY - JOUR

T1 - II. Correlations between secondary structure stability and mutation frequency during somatic hypermutation

AU - Wright, Barbara E.

AU - Schmidt, Karen H.

AU - Davis, Nick

AU - Hunt, Aaron T.

AU - Minnick, Michael F.

N1 - Funding Information: This research was funded by NIH grant R01CA099242 and the Stella Duncan Memorial Research Institute.

PY - 2008/8

Y1 - 2008/8

N2 - The role of secondary structures and base mutability at different levels of transcription and supercoiling is analyzed in variable region antibody genes VH5, VH94 and VH186.2. The data are consistent with a model of somatic hypermutation in which increasing levels of transcription and secondary structure stability correlate with the initial formation of successive mutable sites. Encoded differences exist in stem length and the number of GC pairs at low versus high levels of transcription in CDRs. These circumstances simplify the complexities of coordinating mutagenesis by confining this process to each mutable site successively, as they form in response to increasing levels of transcription during affinity maturation.

AB - The role of secondary structures and base mutability at different levels of transcription and supercoiling is analyzed in variable region antibody genes VH5, VH94 and VH186.2. The data are consistent with a model of somatic hypermutation in which increasing levels of transcription and secondary structure stability correlate with the initial formation of successive mutable sites. Encoded differences exist in stem length and the number of GC pairs at low versus high levels of transcription in CDRs. These circumstances simplify the complexities of coordinating mutagenesis by confining this process to each mutable site successively, as they form in response to increasing levels of transcription during affinity maturation.

KW - Computer model

KW - DNA secondary structures

KW - Somatic hypermutation

KW - Transcription

KW - VH genes

UR - https://www.scopus.com/pages/publications/46749142830

U2 - 10.1016/j.molimm.2008.05.012

DO - 10.1016/j.molimm.2008.05.012

M3 - Article

C2 - 18584870

AN - SCOPUS:46749142830

SN - 0161-5890

VL - 45

SP - 3600

EP - 3608

JO - Molecular Immunology

JF - Molecular Immunology

IS - 13

ER -

II. Correlations between secondary structure stability and mutation frequency during somatic hypermutation

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