Unknown

Dataset Information

0

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


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.

SUBMITTER: Zan H 

PROVIDER: S-EPMC4625537 | biostudies-other | 2003 Jun

REPOSITORIES: biostudies-other

altmetric image

Publications

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

Zan Hong H   Wu Xiaoping X   Komori Atsumasa A   Holloman William K WK   Casali Paolo P  

Immunity 20030601 6


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-induce  ...[more]

Similar Datasets

| S-EPMC7492393 | biostudies-literature
| S-EPMC3496973 | biostudies-literature
| S-EPMC2790616 | biostudies-literature
2010-05-27 | E-GEOD-1905 | biostudies-arrayexpress
| S-EPMC2926616 | biostudies-literature
| S-EPMC380999 | biostudies-literature
2014-03-23 | E-MTAB-1241 | biostudies-arrayexpress
2004-12-22 | GSE1905 | GEO
| S-EPMC6786661 | biostudies-literature
| S-EPMC4030556 | biostudies-literature