Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024591 (
malignant hyperthermia
)
2,353
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It is proposed that mismatch repair (MMR) mediates the cytotoxic effects of DNA damaging agents by exerting a futile repair pathway which leads to double strand breaks (DSBs). Previous reports indicate that the sensitivity of cells defective in homologous recombination (HR) to DNA alkylation is reduced by defects in MMR genes. We have assessed the contribution of different MMR genes to the processing of alkylation damage
in vivo
. We have directly visualized recombination complexes formed upon DNA damage using fluorescent protein (FP) fusions. We find that
msh
6 mutants are more resistant than wild type cells to
MNNG
, and that an
msh
6 mutation rescues the sensitivity of
rad
52 strains more efficiently than an
msh
3 mutation. Analysis of RAD52-GFP tagged strains indicate that
MNNG
increases repair foci formation, and that the inactivation of the
MHS
2 and MSH6 genes but not the MSH3 gene result in a reduction of the number of foci formed. In addition, in the absence of HR, NHEJ could process the
MNNG
-induced DSBs as indicated by the formation of NHEJ-GFP tagged foci. These data suggest that processing of the alkylation damage by MMR, mainly by MSH2-MSH6, is required for recruitment of recombination proteins to the damage site for repair.
...
PMID:The Role of DNA Mismatch Repair and Recombination in the Processing of DNA Alkylating Damage in Living Yeast Cells. 2690 Apr 94
