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.
- Author:
Su Man LEE
1
;
Min S PARK
Author Information
1. Genome Research Center for Reproductive Medicine and Infertility, CHA General Hospital, College of Medicine, Pochon University, Seoul, Korea. suman@cha.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
trinucleotide repeats;
trinucleotide expansion;
genetics;
neuromuscular direases;
DNA replication
- MeSH:
Base Sequence;
DNA, Single-Stranded/*metabolism;
Endodeoxyribonucleases/genetics/*metabolism;
Flap Endonucleases;
Gene Expression Regulation;
Genetic Diseases, Inborn/*genetics;
Human;
Nucleic Acid Conformation;
Trinucleotide Repeat Expansion;
*Trinucleotide Repeats
- From:Experimental & Molecular Medicine
2002;34(4):313-317
- CountryRepublic of Korea
- Language:English
-
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.
