期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 377, 期 3, 页码 679-690出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2007.10.074
关键词
FEN-1; C-terminus; protein-protein interaction
资金
- NCI NIH HHS [R01CA073764, F32 CA117236-02, R01 CA073764-12, R01CA081063, R01CA085344, F32 CA117236, R01 CA085344, R01 CA073764] Funding Source: Medline
- NIAMS NIH HHS [F31 AR051615] Funding Source: Medline
Flap endonuclease-1 (FEN-1) is a multifunctional and structure-specific nuclease that plays a critical role in maintaining human genome stability through RNA primer removal, long-patch base excision repair, resolution of DNA secondary structures and stalled DNA replication forks, and apoptotic DNA fragmentation. How FEN-1 is involved in multiple pathways, of which some are seemingly contradictory, is of considerable interest. To date, at least 20 proteins are known to interact with FEN-1; some form distinct complexes that affect one or more FEN-1 activities presumably to direct FEN-1 to a particular DNA metabolic pathway. FEN-1 consists of a nuclease core domain and a C-terminal extension. While the core domain harbors the nuclease activity, the C-terminal extension may be important for protein-protein interactions. Here, we have truncated or mutated the C-terminus of FEN-1 to identify amino acid residues that are critical for interaction with five proteins representing roles in different DNA replication and repair pathways. We found with all five proteins that the C-terminus is important for binding and that each protein uses a subset of amino acid residues. Replacement of one or more residues with an alanine in many cases leads to the complete loss of interaction, which may consequently lead to severe biological defects in mammals. (C) 2007 Elsevier Ltd. All rights reserved.
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