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Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding
It is reported that FEN1 is methylated at arginine residues, primarily at R192, which leads to a defect in Okazaki fragment maturation, a delay of cell cycle progression, impairment of DNA repair, and high frequency of genome-wide mutations.
Overexpression and Hypomethylation of Flap Endonuclease 1 Gene in Breast and Other Cancers
It is shown that F EN1 is significantly up-regulated in multiple cancers and the aberrant expression of FEN1 is associated with hypomethylation of the CpG island within the FEN2 promoter in tumor cells.
Fen1 mutations result in autoimmunity, chronic inflammation and cancers
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.
Mammalian DNA2 helicase/nuclease cleaves G‐quadruplex DNA and is required for telomere integrity
The genetic, cytological, and biochemical results suggest that mammalian DNA2 reduces replication stress at telomeres, thereby preserving genome stability and suppressing cancer development, and that this may involve, at least in part, nucleolytic processing of telomeric G4.
Human DNA polymerase β polymorphism, Arg137Gln, impairs its polymerase activity and interaction with PCNA and the cellular base excision repair capacity
It is shown that a polymorphism encoding an arginine to glutamine substitution, R137Q, has lower polymerase activity, which indicates that polymorphisms in base excision repair genes may contribute to the onset and development of cancers.
Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression
Formation of polyploidy, which is often observed in human cancers, leads to overexpression of BRCA1, p19arf and other DNA repair genes in FEN1 mutant cells, which triggers SSB repair and non-homologous end joining pathways to increase DNA repair activity, but at the cost of frequent chromosomal translocations.
Mutational spectra of p53 in geographically localized esophageal squamous cell carcinoma groups in China
Esophageal carcinoma is a particularly interesting tumor because of the dramatic difference in its incidence and geographic distribution among populations of similar ethnic origin. Epidemiologic data
Nucleolar Localization and Dynamic Roles of Flap Endonuclease 1 in Ribosomal DNA Replication and Damage Repair
It is found that FEN1 is superaccumulated in the nucleolus and plays a role in the resolution of stalled DNA replication forks formed at the sites of natural replication fork barriers.