Dimerization of MLH1 and PMS2 Limits Nuclear Localization of MutLα
نویسندگان
چکیده
منابع مشابه
Dimerization and nuclear localization of ku proteins.
Ku, a heterodimer of Ku70 and Ku80, plays a key role in multiple nuclear processes, e.g. DNA repair, chromosome maintenance, and transcription regulation. Heterodimerization is essential for Ku-dependent DNA repair in vivo, although its role is poorly understood. Some lines of evidence suggest that heterodimerization is required for the stabilization of Ku70 and Ku80. Here we show that the hete...
متن کاملInteraction of proliferating cell nuclear antigen with PMS2 is required for MutLα activation and function in mismatch repair.
Eukaryotic MutLα (mammalian MLH1-PMS2 heterodimer; MLH1-PMS1 in yeast) functions in early steps of mismatch repair as a latent endonuclease that requires a mismatch, MutSα/β, and DNA-loaded proliferating cell nuclear antigen (PCNA) for activation. We show here that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends...
متن کاملDifferent mutator phenotypes in Mlh1- versus Pms2-deficient mice.
Deficiencies in DNA mismatch repair (MMR) result in increased mutation rates and cancer risk in both humans and mice. Mouse strains homozygous for knockouts of either the Pms2 or Mlh1 MMR gene develop cancer but exhibit very different tumor spectra; only Mlh1(-/-) animals develop intestinal tumors. We carried out a detailed study of the microsatellite mutation spectra in each knockout strain. F...
متن کاملMutLα Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia
BACKGROUND Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics o...
متن کاملC-Terminal Fluorescent Labeling Impairs Functionality of DNA Mismatch Repair Proteins
The human DNA mismatch repair (MMR) process is crucial to maintain the integrity of the genome and requires many different proteins which interact perfectly and coordinated. Germline mutations in MMR genes are responsible for the development of the hereditary form of colorectal cancer called Lynch syndrome. Various mutations mainly in two MMR proteins, MLH1 and MSH2, have been identified so far...
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ژورنال
عنوان ژورنال: Molecular and Cellular Biology
سال: 2003
ISSN: 0270-7306,1098-5549
DOI: 10.1128/mcb.23.9.3320-3328.2003