A Role for the MutL Mismatch Repair Mlh3 Protein in Immunoglobulin Class Switch DNA Recombination and Somatic Hypermutation

A role for Mlh3 in somatic hypermutation.

Somatic hypermutation (SHM) and class switch recombination (CSR) allow B cells to make high affinity antibodies of various isotypes. Both processes are initiated by activation-induced cytidine deaminase (AID) to generate dG:dU mismatches in the immunoglobulin genes that are resolved differently in SHM and CSR to introduce point mutations and recombination, respectively. The MutL homolog MLH3 ha...

Somatic Hypermutation, Transcription, and DNA Mismatch Repair

hypermutation, suggesting that cis-acting sequences outside the mutable region regulate and target mutation. However, almost nothing is known about the detailed molecular mechanisms or transacting proteins that are responsible for V-region hypermutation. Because the mutational process begins just downstream of the promoter and requires transcriptional en-hancers (Neuberger et al., 1998), it has...

Somatic Hypermutation and Class Switch Recombination in Msh6

A Role for Msh6 But Not Msh3 in Somatic Hypermutation and Class Switch Recombination

Somatic hypermutation is initiated by activation-induced cytidine deaminase (AID), and occurs in several kilobases of DNA around rearranged immunoglobulin variable (V) genes and switch (S) sites before constant genes. AID deaminates cytosine to uracil, which can produce mutations of C:G nucleotide pairs, and the mismatch repair protein Msh2 participates in generating substitutions of downstream...

Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation

Class switch recombination (CSR) and somatic hypermutation (SHM) are mechanistically related processes initiated by activation-induced cytidine deaminase. Here, we have studied the role of ataxia telangiectasia and Rad3-related protein (ATR) in CSR by analyzing the recombinational junctions, resulting from in vivo switching, in cells from patients with mutations in the ATR gene. The proportion ...