Related Experiment Video
Updated: Jun 6, 2026
28:15
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT
Jennifer L Wilding1, Simon McGowan, Ying Liu
1Cancer and Immunogenetics Laboratory, The Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
Summary
Replication error deficient (RER+) colorectal cancers exhibit altered gene expression due to mutations in 3'UTR repeat sequences. This impacts mRNA stability, differentiating them from RER- cancers.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Replication error deficient (RER+) colorectal cancers are defined by DNA mismatch repair system inactivation.
- These cancers accumulate mutations in repetitive sequences and have distinct pathologies.
- Regulatory sequences, including 3'UTRs, control mRNA processing and stability.
Purpose of the Study:
- To investigate the molecular basis for differential gene expression in RER+ versus RER- colorectal cancers.
- To determine the role of 3'UTR repeat sequences in RER+ colorectal cancer gene expression profiles.
Main Methods:
- Microarray analysis of RER+ and RER- colorectal cancer cell lines.
- Analysis of mononucleotide repeat sequences in 5'UTRs, 3'UTRs, and coding sequences.
- Sequence analysis of 3'UTRs in differentially expressed genes.
Main Results:
- Striking differences in expression profiles were observed between RER+ and RER- colorectal cancer cell lines.
- A significant enrichment of genes with long 3'UTR T repeats (>11 bp) was found in differentially expressed genes in RER+ cancers.
- Deletions in these 3'UTR repeats were present in RER+ cell lines for most differentially expressed genes.
Conclusions:
- Deregulation of mRNA stability, caused by mutations in 3'UTR repeat sequences, underlies the distinct gene expression profiles in RER+ colorectal cancers.
- The findings highlight the importance of 3'UTR regulatory elements in colorectal cancer development and progression.
Related Concept Videos
01:20Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
01:36Mismatch Repair
Overview
02:46Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
01:31Proofreading
Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore, it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors During Replication are Corrected by the DNA Polymerase Enzyme
Errors During Replication are Corrected by the DNA Polymerase Enzyme
01:43Proofreading
Synthesis of new DNA molecules starts when DNA polymerase links nucleotides together in a sequence that is complementary to the template DNA strand. DNA polymerase has a higher affinity for the correct base to ensure fidelity in DNA replication. The DNA polymerase furthermore proofreads during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.Errors during Replication Are Corrected by the DNA Polymerase EnzymeGenomic DNA is synthesized in...
01:38Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...