This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Larsen, E.
Right arrow Articles by Klungland, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Larsen, E.
Right arrow Articles by Klungland, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2003, p. 5346-5353, Vol. 23, No. 15
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.15.5346-5353.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Proliferation Failure and Gamma Radiation Sensitivity of Fen1 Null Mutant Mice at the Blastocyst Stage

Elisabeth Larsen, Christine Gran, Barbro Elisabet Sæther, Erling Seeberg, and Arne Klungland*

Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, The National Hospital, University of Oslo, 0027 Oslo, Norway

Received 13 March 2003/ Returned for modification 10 April 2003/ Accepted 8 May 2003

Flap endonuclease 1 (FEN1) has been shown to remove 5' overhanging flap intermediates during base excision repair and to process the 5' ends of Okazaki fragments during lagging-strand DNA replication in vitro. To assess the in vivo role of the mammalian enzyme in repair and replication, we used a gene-targeting approach to generate mice lacking a functional Fen1 gene. Heterozygote animals appear normal, whereas complete depletion of FEN1 causes early embryonic lethality. Fen1-/- blastocysts fail to form inner cell mass during cellular outgrowth, and a complete inactivation of DNA synthesis in giant cells of blastocyst outgrowth was observed. Exposure of Fen1-/- blastocysts to gamma radiation caused extensive apoptosis, implying an essential role for FEN1 in the repair of radiation-induced DNA damage in vivo. Our data thus provide in vivo evidence for an essential function of FEN1 in DNA repair, as well as in DNA replication.

* Corresponding author. Mailing address: Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, The National Hospital, University of Oslo, 0027 Oslo, Norway. Phone: 47-23074069. Fax: 47-23074061. E-mail: aklungla{at}labmed.uio.no.

Molecular and Cellular Biology, August 2003, p. 5346-5353, Vol. 23, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.15.5346-5353.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schurman, S. H., Hedayati, M., Wang, Z., Singh, D. K., Speina, E., Zhang, Y., Becker, K., Macris, M., Sung, P., Wilson, D. M. III, Croteau, D. L., Bohr, V. A. (2009). Direct and indirect roles of RECQL4 in modulating base excision repair capacity. Hum Mol Genet 18: 3470-3483 [Abstract] [Full Text]  
  • Finger, L. D., Blanchard, M. S., Theimer, C. A., Sengerova, B., Singh, P., Chavez, V., Liu, F., Grasby, J. A., Shen, B. (2009). The 3'-Flap Pocket of Human Flap Endonuclease 1 Is Critical for Substrate Binding and Catalysis. J. Biol. Chem. 284: 22184-22194 [Abstract] [Full Text]  
  • Cho, I.-t., Kim, D.-h., Kang, Y.-H., Lee, C.-H., Amangyelid, T., Nguyen, T. A., Hurwitz, J., Seo, Y.-S. (2009). Human Replication Factor C Stimulates Flap Endonuclease 1. J. Biol. Chem. 284: 10387-10399 [Abstract] [Full Text]  
  • Maynard, S., Schurman, S. H., Harboe, C., de Souza-Pinto, N. C., Bohr, V. A. (2009). Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis 30: 2-10 [Abstract] [Full Text]  
  • Liu, P., Qian, L., Sung, J.-S., de Souza-Pinto, N. C., Zheng, L., Bogenhagen, D. F., Bohr, V. A., Wilson, D. M. III, Shen, B., Demple, B. (2008). Removal of Oxidative DNA Damage via FEN1-Dependent Long-Patch Base Excision Repair in Human Cell Mitochondria. Mol. Cell. Biol. 28: 4975-4987 [Abstract] [Full Text]  
  • Kim, I., Hur, N. W., Shin, H. D., Park, B. L., Cheong, H. S., Bae, S.-C. (2008). Associations of DNase IV polymorphisms with autoantibodies in patients with systemic lupus erythematosus. Rheumatology (Oxford) 47: 996-999 [Abstract] [Full Text]  
  • Larsen, E., Kleppa, L., Meza, T. J., Meza-Zepeda, L. A., Rada, C., Castellanos, C. G., Lien, G. F., Nesse, G. J., Neuberger, M. S., Laerdahl, J. K., William Doughty, R., Klungland, A. (2008). Early-Onset Lymphoma and Extensive Embryonic Apoptosis in Two Domain-Specific Fen1 Mice Mutants. Cancer Res. 68: 4571-4579 [Abstract] [Full Text]  
  • Schultz-Norton, J. R., Walt, K. A., Ziegler, Y. S., McLeod, I. X., Yates, J. R., Raetzman, L. T., Nardulli, A. M. (2007). The Deoxyribonucleic Acid Repair Protein Flap Endonuclease-1 Modulates Estrogen-Responsive Gene Expression. Mol. Endocrinol. 21: 1569-1580 [Abstract] [Full Text]  
  • Zheng, L., Dai, H., Qiu, J., Huang, Q., Shen, B. (2007). Disruption of the FEN-1/PCNA Interaction Results in DNA Replication Defects, Pulmonary Hypoplasia, Pancytopenia, and Newborn Lethality in Mice. Mol. Cell. Biol. 27: 3176-3186 [Abstract] [Full Text]  
  • Sharma, S., Sommers, J. A., Gary, R. K., Friedrich-Heineken, E., Hubscher, U., Brosh, R. M. Jr (2005). The interaction site of Flap Endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA. Nucleic Acids Res 33: 6769-6781 [Abstract] [Full Text]  
  • Holen, T., Moe, S. E., Sorbo, J. G., Meza, T. J., Ottersen, O. P., Klungland, A. (2005). Tolerated wobble mutations in siRNAs decrease specificity, but can enhance activity in vivo. Nucleic Acids Res 33: 4704-4710 [Abstract] [Full Text]  
  • Kikuchi, K., Taniguchi, Y., Hatanaka, A., Sonoda, E., Hochegger, H., Adachi, N., Matsuzaki, Y., Koyama, H., van Gent, D. C., Jasin, M., Takeda, S. (2005). Fen-1 Facilitates Homologous Recombination by Removing Divergent Sequences at DNA Break Ends. Mol. Cell. Biol. 25: 6948-6955 [Abstract] [Full Text]  
  • Zheng, P., Schramm, R. D., Latham, K. E. (2005). Developmental Regulation and In Vitro Culture Effects on Expression of DNA Repair and Cell Cycle Checkpoint Control Genes in Rhesus Monkey Oocytes and Embryos. Biol. Reprod. 72: 1359-1369 [Abstract] [Full Text]  
  • Moritoh, S., Miki, D., Akiyama, M., Kawahara, M., Izawa, T., Maki, H., Shimamoto, K. (2005). RNAi-mediated Silencing of OsGEN-L (OsGEN-like), a New Member of the RAD2/XPG Nuclease Family, Causes Male Sterility by Defect of Microspore Development in Rice. Plant Cell Physiol 46: 699-715 [Abstract] [Full Text]  
  • Kim, D.-H., Lee, K.-H., Kim, J.-H., Ryu, G.-H., Bae, S.-H., Lee, B.-C., Moon, K.-Y., Byun, S.-M., Koo, H.-S., Seo, Y.-S. (2005). Enzymatic properties of the Caenorhabditis elegans Dna2 endonuclease/helicase and a species-specific interaction between RPA and Dna2. Nucleic Acids Res 33: 1372-1383 [Abstract] [Full Text]  
  • Wang, W., Bambara, R. A. (2005). Human Bloom Protein Stimulates Flap Endonuclease 1 Activity by Resolving DNA Secondary Structure. J. Biol. Chem. 280: 5391-5399 [Abstract] [Full Text]  
  • Morita, M., Stamp, G., Robins, P., Dulic, A., Rosewell, I., Hrivnak, G., Daly, G., Lindahl, T., Barnes, D. E. (2004). Gene-Targeted Mice Lacking the Trex1 (DNase III) 3'->5' DNA Exonuclease Develop Inflammatory Myocarditis. Mol. Cell. Biol. 24: 6719-6727 [Abstract] [Full Text]  
  • Zhang, J., Dong, M., Li, L., Fan, Y., Pathre, P., Dong, J., Lou, D., Wells, J. M., Olivares-Villagomez, D., Van Kaer, L., Wang, X., Xu, M. (2003). Endonuclease G is required for early embryogenesis and normal apoptosis in mice. Proc. Natl. Acad. Sci. USA 100: 15782-15787 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»