Fen1 mutations result in autoimmunity, chronic inflammation and cancers.

Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Research Abstract Details 

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Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Abstract Text:

Li Zheng,Huifang Dai,Mian Zhou,Mei Li,Purnima Singh,Junzhuan Qiu,Walter Tsark,Qin Huang,Kemp Kernstine,Xuemei Zhang,Dongxin Lin,Binghui Shen,

Functional deficiency of the FEN1 gene has been suggested to cause genomic instability and cancer predisposition. We have identified a group of FEN1 mutations in human cancer specimens. Most of these mutations abrogated two of three nuclease activities of flap endonuclease 1 (FEN1). To demonstrate the etiological significance of these somatic mutations, we inbred a mouse line harboring the E160D mutation representing mutations identified in human cancers. Selective elimination of nuclease activities led to frequent spontaneous mutations and accumulation of incompletely digested DNA fragments in apoptotic cells. The mutant mice were predisposed to autoimmunity, chronic inflammation and cancers. The mutator phenotype results in the initiation of cancer, whereas chronic inflammation promotes the cancer progression. The current work exemplifies the approach of studying the mechanisms of individual polymorphisms and somatic mutations in cancer development, and may serve as a reference in developing new therapeutic regimens through the suppression of inflammatory responses.

Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Publishing Authors By Initials

L Zheng,H Dai,M Zhou,M Li,P Singh,J Qiu,W Tsark,Q Huang,K Kernstine,X Zhang,D Lin,B Shen,

For similar neoplasms research abstracts see: neoplasms research

PUBMED ID PMID:

MEDLINE DATE:

Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature medicine

VOLUME: 13

Page Numbers: 812-9

Journal Abbreviation: Nat. Med.

ISSN: 1078-8956

DAY: 24

MONTH: 06

YEAR: 2007

Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502015

Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Keywords Mesh Terms:

KEYWORDS: Neoplasms

MESH TERMS: metabolism

Chemical & Substance for Abstract: Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Information

Substance Name: Flap Endonucleases

Registry Number: EC 3.1.-

Grant and Affiliation Information for Fen1 mutations result in autoimmunity, chronic inflammation and cancers.

AFFILIATION: Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, 1500 East Duarte Road, Duarte, California 91010, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01CA073764

ACRONYM: CA

MEDLINETA: Nat Med

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