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Biochemical Genetics

, Volume 43, Issue 5–6, pp 229–237 | Cite as

Local Base Order Influences the Origin of ccr5 Deletions Mediated by DNA Slip Replication

  • Chi-Yu Zhang
  • Ji-Fu Wei
  • Shao-Heng He
Article

Abstract

CCR5 is a seven-transmembrane G-protein-coupled receptor that binds the CC-chemokines including RANTES, eotaxin, MIP-1α and β. CCR5 serves as an essential coreceptor for cell entry of R5 (macrophage-tropic, nonsyncytium-inducing) strains of HIV-1. To date, four deletions have been found in human and primate ccr5. There is little evidence, however, on how these deletion mutations occur. In the present study, we analyzed ccr5 sequences of both mutants and wild type and found that direct repeats flanked the breakpoints of the deletions, suggesting that these deletions resulted from slipped mispairing during DNA replication. Of particular interest was the location of these deletions in or near the regions with higher negative FORS-D values. High negative FORS-D values stand for high stem-loop potential determined by base order and influence mainly the formation of stem-loop structures. Therefore, the particular location of these deletions suggests that the local sequence of bases might be important in the initiation of deletions mediated by DNA slip replication in concert with direct repeats.

Key Words

ccr5 deletion direct repeats stem-loop potential slip replication 

Abbreviations

CCR5

CC-chemokine receptor 5

RANTES

regulated on activation, normal T cell expressed and secreted

MIP

macrophage inflammatory protein

HIV-1

human immunodeficiency virus type 1

ORF

open reading frame

AIDS

acquired immunodeficiency syndrome

FORS-D

folding of randomized sequence difference

FONS

folding of natural sequence

FORS-M

folding of randomized sequence mean

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Allergy and Inflammation Research InstituteMedical College of Shantou UniversityShantou, GuangdongP.R. China
  2. 2.Department of Biochemistry and Molecular Biology, School of Medical TechnologyJiangsu UniversityZhenjiang, JiangsuP.R. China

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