AID-dependent generation of resected double-strand DNA breaks and recruitment of Rad52/Rad51 in somatic hypermutation. Academic Article uri icon

Overview

abstract

  • Somatic hypermutation (SHM) of immunoglobulin (Ig) genes appears to involve the generation of double-strand DNA breaks (DSBs) and their error-prone repair. Here we show that DSBs occur at a high frequency in unrearranged (germline) Ig variable (V) genes, BCL6 and c-MYC. These DSBs are blunt, target the mutational RGYW/RGY hotspot, and would be resolved through nonhomologous end-joining, as indicated by the presence of Ku70/Ku86 on these DNA ends. Upon CD40-induced expression of activation-induced cytidine deaminase (AID), DSBs increase in frequency and are resected to yield 5'- and 3'-protruding ends in hypermutating rearranged V genes, BCL6 and translocated c-MYC. 3'-protruding ends would direct DSB repair through homologous recombination, as indicated by their exclusive presence in S/G2 and recruitment of Rad52/Rad51, leading to SHM, upon mispair by error-prone DNA polymerases modulated by crosslinking of the B cell receptor for antigen.

publication date

  • June 1, 2003

Research

keywords

  • B-Lymphocytes
  • DNA-Binding Proteins
  • Somatic Hypermutation, Immunoglobulin

Identity

PubMed Central ID

  • PMC4625537

Scopus Document Identifier

  • 0038771252

Digital Object Identifier (DOI)

  • 10.1016/s1074-7613(03)00151-1

PubMed ID

  • 12818155

Additional Document Info

volume

  • 18

issue

  • 6