SLX4 dampens MutSα-dependent mismatch repair.
Nucleic Acids Res
; 50(5): 2667-2680, 2022 03 21.
Article
em En
| MEDLINE
| ID: mdl-35166826
The tumour suppressor SLX4 plays multiple roles in the maintenance of genome stability, acting as a scaffold for structure-specific endonucleases and other DNA repair proteins. It directly interacts with the mismatch repair (MMR) protein MSH2 but the significance of this interaction remained unknown until recent findings showing that MutSß (MSH2-MSH3) stimulates in vitro the SLX4-dependent Holliday junction resolvase activity. Here, we characterize the mode of interaction between SLX4 and MSH2, which relies on an MSH2-interacting peptide (SHIP box) that drives interaction of SLX4 with both MutSß and MutSα (MSH2-MSH6). While we show that this MSH2 binding domain is dispensable for the well-established role of SLX4 in interstrand crosslink repair, we find that it mediates inhibition of MutSα-dependent MMR by SLX4, unravelling an unanticipated function of SLX4.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a DNA
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Endonucleases
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Proteína 2 Homóloga a MutS
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Reparo de Erro de Pareamento de DNA
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article