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The multifaceted mismatch-repair system
  • J. Jiricny
  • Biology
    Nature Reviews Molecular Cell Biology
  • 1 May 2006
This article reviews the current understanding of this multifaceted DNA-repair system in human cells and investigates how MMR status affects meiotic and mitotic recombination, DNA-damage signalling, apoptosis and cell-type-specific processes.
Transcriptome Profile of Human Colorectal Adenomas
Significant differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas, and KIAA1199 was identified as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenOMatous transformation.
Modification of the human thymine‐DNA glycosylase by ubiquitin‐like proteins facilitates enzymatic turnover
It is shown that TDG interacts with and is covalently modified by the ubiquitin‐like proteins SUMO‐1 andsumO‐2/3, and SUMO conjugation dramatically reduces the DNA substrate and AP site binding affinity of TDG, and this is associated with a significant increase in enzymatic turnover in reactions with a G·U substrate and the loss of G·T processing activity.
Mismatch repair-dependent G2 checkpoint induced by low doses of SN1 type methylating agents requires the ATR kinase.
It is shown that MNNG treatment induced a cell cycle arrest that was absolutely dependent on functional MMR, and the response of human MMR-proficient and MMR-deficient cells to low concentrations of the prototypic methylating agent N-methyl-N'-nitro-N-nitrosoguanidine.
hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci.
It is postulate that PCNA plays a role in repair initiation by guiding the mismatch repair proteins to free termini in the newly replicated DNA strands.
The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites
MBD4, an unrelated mammalian protein that contains a methyl-CpG binding domain, can also efficiently remove thymine or uracil from a mismatches CpG site in vitro and the combined specificities of binding and catalysis indicate that this enzyme may function to minimize mutation at methyl-GpG.
Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability
It is shown that TDG contributes to the maintenance of active and bivalent chromatin throughout cell differentiation, facilitating a proper assembly of chromatin-modifying complexes and initiating base excision repair to counter aberrant de novo methylation, and has evolved to provide epigenetic stability in lineage committed cells.
Expression of the MutL homologue hMLH3 in human cells and its role in DNA mismatch repair.
It is shown that the hMLH1/hMLH3 heterodimer, hMutLgamma, can also assist in the repair of base-base mismatches and single extrahelical nucleotides in vitro.