Multiple but dissectible functions of FEN-1 nucleases in nucleic acid processing, genome stability and diseases
✍ Scribed by Binghui Shen; Purnima Singh; Ren Liu; Junzhuan Qiu; Li Zheng; L. David Finger; Steve Alas
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 402 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0265-9247
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✦ Synopsis
Abstract
__F__lap __E__ndo__N__uclease‐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. BioEssays 27:717–729, 2005. © 2005 Wiley Periodicals, Inc.