Generation and repair of AID-initiated DNA lesions in B lymphocytes

Front Med. 2014 Jun;8(2):201-16. doi: 10.1007/s11684-014-0324-4. Epub 2014 Apr 21.

Abstract

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

Publication types

  • Review

MeSH terms

  • AICDA (Activation-Induced Cytidine Deaminase)
  • Animals
  • Antibody Diversity / physiology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology*
  • Cytidine Deaminase / metabolism
  • Cytidine Deaminase / physiology*
  • DNA Damage / physiology*
  • DNA Repair / physiology*
  • Immunoglobulin Class Switching / physiology
  • Point Mutation / physiology

Substances

  • AICDA (Activation-Induced Cytidine Deaminase)
  • Cytidine Deaminase