Unknown

Dataset Information

0

Malaria drug resistance is associated with defective DNA mismatch repair.

ABSTRACT: Malarial parasites exhibit striking genetic plasticity, a hallmark of which is an ever-increasing rate of resistance to new drugs, especially in Southeast Asia where multi-drug resistance (MDR) threatens the last line of antimalarial drugs, the artesunate compounds. Previous studies quantified the accelerated resistance to multiple drugs (ARMD) phenomenon, but the underpinning mechanism(s) remains unknown. We utilize a forward genetic assay to investigate a new hypothesis that defective DNA mismatch repair (MMR) contributes to the development of MDR by Plasmodium falciparum parasites. We report that two ARMD parasites, W2 and Dd2, have defective MMR, as do the chloroquine-resistant parasites T9-94, 7C12, and 7G8. By contrast, the chloroquine-sensitive parasites HB3, D6 and 3D7 were MMR proficient. Interestingly, W2 was unable to repair substrates with a strand break located 3' to the mismatch, which is attributable to a large observed decrease in PfMutL? content. These data imply that antimalarial drug resistance can result from defective MMR.

SUBMITTER: Castellini MA 

PROVIDER: S-EPMC3075314 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Malaria drug resistance is associated with defective DNA mismatch repair.

Castellini Meryl A MA   Buguliskis Jeffrey S JS   Casta Louis J LJ   Butz Charles E CE   Clark Alan B AB   Kunkel Thomas A TA   Taraschi Theodore F TF  

Molecular and biochemical parasitology 20110221 2

Malarial parasites exhibit striking genetic plasticity, a hallmark of which is an ever-increasing rate of resistance to new drugs, especially in Southeast Asia where multi-drug resistance (MDR) threatens the last line of antimalarial drugs, the artesunate compounds. Previous studies quantified the accelerated resistance to multiple drugs (ARMD) phenomenon, but the underpinning mechanism(s) remains unknown. We utilize a forward genetic assay to investigate a new hypothesis that defective DNA mism  ...[more]

Similar Datasets

Unknown The role of DNA mismatch repair in generating genetic diversity and drug resistance in malaria parasites.
| S-EPMC3683857 | biostudies-literature
Unknown hMRE11 deficiency leads to microsatellite instability and defective DNA mismatch repair.
| S-EPMC1299302 | biostudies-literature
Unknown Both microsatellite length and sequence context determine frameshift mutation rates in defective DNA mismatch repair.
| S-EPMC2912546 | biostudies-literature
Unknown Identification of colorectal cancers with defective DNA damage repair by immunohistochemical profiling of mismatch repair proteins, CDX2 and BRCA1.
| S-EPMC7484731 | biostudies-literature
Unknown DNA repair pathways in trypanosomatids: from DNA repair to drug resistance.
| S-EPMC3957735 | biostudies-literature
Unknown MonoSeq Variant Caller Reveals Novel Mononucleotide Run Indel Mutations in Tumors with Defective DNA Mismatch Repair.
| S-EPMC5021604 | biostudies-literature
Unknown Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patients.
| S-EPMC2855300 | biostudies-literature
Unknown Flanking sequence specificity determines coding microsatellite heteroduplex and mutation rates with defective DNA mismatch repair (MMR).
| S-EPMC4028169 | biostudies-literature
Unknown Mutation rates of TGFBR2 and ACVR2 coding microsatellites in human cells with defective DNA mismatch repair.
| S-EPMC2565065 | biostudies-literature
Unknown Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers.
| S-EPMC156300 | biostudies-literature