Multiple but dissectible functions of FEN-1 nucleases in nucleic acid processing, genome stability and diseases.
Flap EndoNuclease-1 (FEN-1) is a multifunctional and structure-specific nuclease involved in nucleic acid processing pathways. It plays a critical role in maintaining human genome stability through RNA primer removal, long-patch base excision repair and resolution of dinucleotide and trinucleotide repeat secondary structures. In addition to its flap endonuclease (FEN) and nick exonuclease (EXO) activities, a new gap endonuclease (GEN) activity has been characterized. This activity may be important in apoptotic DNA fragmentation and in resolving stalled DNA replication forks. The multiple functions of FEN-1 are regulated via several means, including formation of complexes with different protein partners, nuclear localization in response to cell cycle or DNA damage and post-translational modifications. Its functional deficiency is predicted to cause genetic diseases, including Huntington's disease, myotonic dystrophy and cancers. This review summarizes the knowledge gained through efforts in the past decade to define its structural elements for specific activities and possible pathological consequences of altered functions of this multirole player.
Shen
Binghui
B
Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA. bshen@coh.org
Singh
Purnima
P
Liu
Ren
R
Qiu
Junzhuan
J
Zheng
Li
L
Finger
L David
LD
Alas
Steve
S
D020816:Amino Acid Motifs; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D004720:Endonucleases / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D045585:Flap Endonucleases / Q000737:chemistry / Q000502:physiology*; D016678:Genome; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D009135:Muscular Diseases / Q000378:metabolism; D009696:Nucleic Acids / Q000737:chemistry; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000737:chemistry; D013329:Structure-Activity Relationship
D017931:DNA Primers; D009696:Nucleic Acids; D018809:Proliferating Cell Nuclear Antigen; D012313:RNA; D004247:DNA; D004720:Endonucleases; D005092:Exonucleases; D045585:Flap Endonucleases