Fen-1 facilitates homologous recombination by removing divergent sequences at DNA break ends Journal Article
| Authors: | Kikuchi, K.; Taniguchi, Y.; Hatanaka, A.; Sonoda, E.; Hochegger, H.; Adachi, N.; Matsuzaki, Y.; Koyama, H.; van Gent, D. C.; Jasin, M.; Takeda, S. |
| Article Title: | Fen-1 facilitates homologous recombination by removing divergent sequences at DNA break ends |
| Abstract: | Homologous recombination (HR) requires nuclease activities at multiple steps, but the contribution of individual nucleases to the processing of double-strand DNA ends at different stages of HR has not been clearly defined. We used chicken DT40 cells to investigate the role of flap endonuclease 1 (Fen-1) in HR. FEN-1-deficient cells exhibited a significant decrease in the efficiency of immunoglobulin gene conversion while being proficient in recombination between sister chromatids, suggesting that Fen-1 may play a role in HR between sequences of considerable divergence. To clarify whether sequence divergence at DNA ends is truly the reason for the observed HR defect in FEN-1 -/- cells we inserted a unique I-SceI restriction site in the genome and tested various donor and recipient HR substrates. We found that the efficiency of HR-mediated DNA repair was indeed greatly diminished when divergent sequences were present at the DNA break site. We conclude that Fen-1 eliminates heterologous sequences at DNA damage site and facilitates DNA repair by HR. Copyright © 2005, American Society for Microbiology. All Rights Reserved. |
| Keywords: | unclassified drug; mutation; nonhuman; flow cytometry; animal cell; animals; dna damage; homologous recombination; cell cycle; dna repair; sister chromatid; enzyme activity; transfection; time factors; dna strand breakage; gene conversion; dna; double stranded dna; immunoglobulin gene; molecular sequence data; kinetics; recombination, genetic; nucleotide sequence; sister chromatid exchange; nuclease; base sequence; plasmids; genome; models, genetic; dna sequence; flap endonuclease 1; flap endonucleases; sequence homology, nucleic acid; dna, complementary; chickens; gamma rays; chicken; deoxyribonucleases, type ii site-specific |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 25 |
| Issue: | 16 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2005-08-01 |
| Start Page: | 6948 |
| End Page: | 6955 |
| Language: | English |
| DOI: | 10.1128/mcb.25.16.6948-6955.2005 |
| PUBMED: | 16055708 |
| PROVIDER: | scopus |
| PMCID: | PMC1190240 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 25" - "Export Date: 24 October 2012" - "CODEN: MCEBD" - "Molecular Sequence Numbers: GENBANK: AB063480;" - "Source: Scopus" |
