Noncanonical mismatch repair as a source of genomic instability in human cells.
Mol Cell
; 47(5): 669-80, 2012 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-22864113
ABSTRACT
Mismatch repair (MMR) is a key antimutagenic process that increases the fidelity of DNA replication and recombination. Yet genetic experiments showed that MMR is required for antibody maturation, a process during which the immunoglobulin loci of antigen-stimulated B cells undergo extensive mutagenesis and rearrangements. In an attempt to elucidate the mechanism underlying the latter events, we set out to search for conditions that compromise MMR fidelity. Here, we describe noncanonical MMR (ncMMR), a process in which the MMR pathway is activated by various DNA lesions rather than by mispairs. ncMMR is largely independent of DNA replication, lacks strand directionality, triggers PCNA monoubiquitylation, and promotes recruitment of the error-prone polymerase-η to chromatin. Importantly, ncMMR is not limited to B cells but occurs also in other cell types. Moreover, it contributes to mutagenesis induced by alkylating agents. Activation of ncMMR may therefore play a role in genomic instability and cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Instabilidade Genômica
/
Reparo de Erro de Pareamento de DNA
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article