Human FEN-1 can process the 5'-flap DNA of CTG/CAG triplet repeat derived from human genetic diseases by length and sequence dependent manner
Experimental & Molecular Medicine
;
: 313-317, 2002.
Article
in English
| WPRIM
| ID: wpr-134585
ABSTRACT
Trinucleotide repeat (TNR) instability can cause a variety of human genetic diseases including myotonic dystrophy and Huntington's disease. Recent genetic data show that instability of the CAG/CTG repeat DNA is dependent on its length and replication origin. In yeast, the RAD27 (human FEN-1 homologue) null mutant has a high expansion frequency at the TNR loci. We demonstrate here that FEN-1 processes the 5'-flap DNA of CTG/CAG repeats, which is dependent on the length in vitro. FEN-1 protein can cleave the 5'-flap DNA containing triplet repeating sequence up to 21 repeats, but the activity decreases with increasing size of flap above 11 repeats. In addition, FEN-1 processing of 5'-flap DNA depends on sequence, which play a role in the replication origin-dependent TNR instability. Interestingly, FEN-1 can cleave the 5'-flap DNA of CTG repeats better than CAG repeats possibly through the flap-structure. Our biochemical data of FEN-1's activity with triplet repeat DNA clearly shows length dependence, and aids our understanding on the mechanism of TNR instability.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
DNA, Single-Stranded
/
Base Sequence
/
Gene Expression Regulation
/
Trinucleotide Repeats
/
Trinucleotide Repeat Expansion
/
Flap Endonucleases
/
Endodeoxyribonucleases
/
Genetic Diseases, Inborn
/
Nucleic Acid Conformation
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2002
Type:
Article
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