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Multiple but dissectible functions of FEN‐1 nucleases in nucleic acid processing, genome stability and diseases
Author(s) -
Shen Binghui,
Singh Purnima,
Liu Ren,
Qiu Junzhuan,
Zheng Li,
Finger L. David,
Alas Steve
Publication year - 2005
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.20255
Subject(s) - biology , nuclease , trinucleotide repeat expansion , genetics , nucleic acid , dna , dna repair , genome , myotonic dystrophy , dna replication , rna , computational biology , microbiology and biotechnology , gene , allele
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 f lap e ndo n uclease (FEN) and nick exo nuclease (EXO) activities, a new g ap e ndo n uclease (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.