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Functional regulation of FEN1 nuclease and its link to cancer

Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. FEN1 possesses FEN, 5′-exonuclease and gap-endonuclease activities. The multiple nuclease activities of FEN1 allow it to participate in numerous DNA metabolic pathways, including Okazaki fragment maturation, stall...

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Autores principales: Zheng, Li, Jia, Jia, Finger, L. David, Guo, Zhigang, Zer, Cindy, Shen, Binghui
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035468/
https://www.ncbi.nlm.nih.gov/pubmed/20929870
http://dx.doi.org/10.1093/nar/gkq884
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author Zheng, Li
Jia, Jia
Finger, L. David
Guo, Zhigang
Zer, Cindy
Shen, Binghui
author_facet Zheng, Li
Jia, Jia
Finger, L. David
Guo, Zhigang
Zer, Cindy
Shen, Binghui
author_sort Zheng, Li
collection PubMed
description Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. FEN1 possesses FEN, 5′-exonuclease and gap-endonuclease activities. The multiple nuclease activities of FEN1 allow it to participate in numerous DNA metabolic pathways, including Okazaki fragment maturation, stalled replication fork rescue, telomere maintenance, long-patch base excision repair and apoptotic DNA fragmentation. Here, we summarize the distinct roles of the different nuclease activities of FEN1 in these pathways. Recent biochemical and genetic studies indicate that FEN1 interacts with more than 30 proteins and undergoes post-translational modifications. We discuss how FEN1 is regulated via these mechanisms. Moreover, FEN1 interacts with five distinct groups of DNA metabolic proteins, allowing the nuclease to be recruited to a specific DNA metabolic complex, such as the DNA replication machinery for RNA primer removal or the DNA degradosome for apoptotic DNA fragmentation. Some FEN1 interaction partners also stimulate FEN1 nuclease activities to further ensure efficient action in processing of different DNA structures. Post-translational modifications, on the other hand, may be critical to regulate protein–protein interactions and cellular localizations of FEN1. Lastly, we also review the biological significance of FEN1 as a tumor suppressor, with an emphasis on studies of human mutations and mouse models.
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spelling pubmed-30354682011-02-08 Functional regulation of FEN1 nuclease and its link to cancer Zheng, Li Jia, Jia Finger, L. David Guo, Zhigang Zer, Cindy Shen, Binghui Nucleic Acids Res Survey and Summary Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. FEN1 possesses FEN, 5′-exonuclease and gap-endonuclease activities. The multiple nuclease activities of FEN1 allow it to participate in numerous DNA metabolic pathways, including Okazaki fragment maturation, stalled replication fork rescue, telomere maintenance, long-patch base excision repair and apoptotic DNA fragmentation. Here, we summarize the distinct roles of the different nuclease activities of FEN1 in these pathways. Recent biochemical and genetic studies indicate that FEN1 interacts with more than 30 proteins and undergoes post-translational modifications. We discuss how FEN1 is regulated via these mechanisms. Moreover, FEN1 interacts with five distinct groups of DNA metabolic proteins, allowing the nuclease to be recruited to a specific DNA metabolic complex, such as the DNA replication machinery for RNA primer removal or the DNA degradosome for apoptotic DNA fragmentation. Some FEN1 interaction partners also stimulate FEN1 nuclease activities to further ensure efficient action in processing of different DNA structures. Post-translational modifications, on the other hand, may be critical to regulate protein–protein interactions and cellular localizations of FEN1. Lastly, we also review the biological significance of FEN1 as a tumor suppressor, with an emphasis on studies of human mutations and mouse models. Oxford University Press 2011-02 2010-10-06 /pmc/articles/PMC3035468/ /pubmed/20929870 http://dx.doi.org/10.1093/nar/gkq884 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Survey and Summary
Zheng, Li
Jia, Jia
Finger, L. David
Guo, Zhigang
Zer, Cindy
Shen, Binghui
Functional regulation of FEN1 nuclease and its link to cancer
title Functional regulation of FEN1 nuclease and its link to cancer
title_full Functional regulation of FEN1 nuclease and its link to cancer
title_fullStr Functional regulation of FEN1 nuclease and its link to cancer
title_full_unstemmed Functional regulation of FEN1 nuclease and its link to cancer
title_short Functional regulation of FEN1 nuclease and its link to cancer
title_sort functional regulation of fen1 nuclease and its link to cancer
topic Survey and Summary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035468/
https://www.ncbi.nlm.nih.gov/pubmed/20929870
http://dx.doi.org/10.1093/nar/gkq884
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