Binghui Shen

..All newborn FFAA mutant pups died at birth, likely due to pulmonary hypoplasia and pancytopenia. Collectively, our data demonstrate the importance of the FEN-1/PCNA complex in DNA replication and in the embryonic development of mice...

..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...

..This consequently leads to a defect in Okazaki fragment maturation, a delay in cell cycle progression, impairment of DNA repair and a high frequency of genome-wide mutations...

..The replacement of Ser(187) by Ala, eliminating the only phosphorylation site, retains FEN1 in nucleoli. Both of the mutations cause UV sensitivity, impair cellular UV damage repair capacity, and decline overall cellular survivorship...

..Furthermore, Rad2 and Exo1 complemented the mutator phenotypes and cell cycle defects of rad27 mutant strains to differing extents, suggesting distinct in vivo nucleic acid substrates...

..Furthermore, based on the evidence that GEN activity in complex with WRN protein cleaves hairpin and internal loop substrates, we suggest that the GEN activity may prevent repeat expansions and duplication mutations...

..With longer flap substrates the hnRNP A1 effect is more modest and is suppressed by the addition of RPA. A model is provided to explain the possible in vivo role of this interaction and activity in Okazaki fragment maturation...

..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...

..Together the results indicate that the presence of a 3'-flap is the critical feature for efficient hFEN1 substrate recognition and catalysis...

..Taken together, our studies illustrate an evolutionarily diversified role of hDNA2 in mitochondrial DNA replication and repair in a mammalian system...

..Thus, this study establishes an exemplary case for investigating the biological significance of protein-protein interactions by knock-in of a point mutation rather than knock-out of a whole gene...

..A model is presented to explain how the concerted action of EXO and GEN activities may contribute to resolving structured flaps, thereby preventing their expansion in the genome...

..cerevisiae increases the TUNEL-positive cells and cell survival in response to hydrogen hyperoxide treatment, whereas overexpression of Tat-D facilitates cell death. These results suggest a role of Tat-D in yeast apoptosis...

..The data suggest that RP2 may have previously unrecognized roles as a DNA damage response factor and 3' to 5' exonuclease...

..Taken together, our results suggest distinct roles for two Mg(2+) binding sites in the regulation of mFEN-1 nuclease activities in a mode different from the "two-metal mechanism"...

..R., Hosfield, D. J., Han, S., Qiu, J., Yelent, B., Shen, B., Tainer, J. A. (2004) Cell 116, 39-50) we are able to propose a reasonable model for how the human FEN-1 protein interacts with its DNA substrates...

..These molecular changes rewire DNA damage response and repair gene networks in polyploid tumour cells, enabling them to escape replication stress-induced senescence barriers...

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..Replication protein A facilitates FEN-1 interaction with DNA bubble structures. Human FEN-1, but not the GEN-deficient mutant, E178A, was shown to rescue the defect in resistance to UV and camptothecin in a yeast FEN-1 null mutant...

..These results suggest that, in addition to maintenance of nucleotide pool balance, the human NDK-like proteins may have previously unrecognized roles in DNA nucleolytic processing...

..We conclude that the N-terminal nuclease domain of E. coli polymerase I encodes a functional homologue of FEN-1...

..These data indicate that polymorphisms in base excision repair genes may contribute to the onset and development of cancers...

..The overexpression and promoter hypomethylation of FEN1 may serve as biomarkers for monitoring the progression of cancers...

..On the other hand, mutations that impair editing out of polymerase α incorporation errors result in cancer displaying a strong mutator phenotype...

..The combination of these three point mutations leads to the binding capacity with hMsh2 to nearly zero. Evidence made available in this study sheds light on the pathogenesis of HNPCC, perhaps initiated by an additional MMR gene, hEXO1...

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..Thus, PCNA could have a role in short-patch BER as well as in long-patch BER. Overall, the data reported here show how multiple factors contribute to the activity of MPG in cells...

..These findings may represent a newly identified regulatory mechanism used by cells to ensure precise cell-cycle progression and to prevent transformation...

..Interaction between NEIL1 and FEN-1 is essential for efficient NEIL1-initiated LP-BER. These studies strongly implicate NEIL1 in a distinct subpathway of LP-BER in replicating genomes...

..Our results suggest that CRN-1/FEN-1 may play a critical role in switching the state of cells from DNA replication/repair to DNA degradation during apoptosis...

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..These results strongly suggest that PprI plays a crucial role in regulating multiple DNA repair and protection pathways in response to radiation stress...

..The overexpression of p53 protein may have significance as a prognostic factor for patients with esophageal carcinoma...

..Results showed that the product of gene dra0074 is not involved in RecA induction, but is a regulator of other metabolisms in D. radiodurans...

..These data suggests a dual negative regulatory control of RecX on RecA functions in D. radiodurans...

..The mitochondrial LP-BER pathway likely plays important roles in repairing dL lesions and other oxidative lesions and perhaps in normal mtDNA replication...

..Based on these data, we propose that the C-terminus of Dr1289 has evolved in D. radiodurans to confront the types and amounts of DNA damage...

..The information made available via these studies will be useful in developing new strategies for cancer prevention and treatment. ..

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..Information made available from this systematic study will also establish a relationship between this mechanism, unique mutagenic phenotype(s), and development of genetic diseases. ..

..Completion of this research will not only clarify the molecular mechanisms underlying cancer pathology, but also provide a solid foundation for development of new regimens for cancer therapy. ..

..Completion of this research will not only clarify the molecular mechanisms underlying cancer pathology, but also provide a solid foundation for development of new regimens for cancer therapy. ..

..Completion of this research will not only clarify the molecular mechanisms underlying cancer pathology, but also provide a solid foundation for development of new regimens for cancer therapy. ..

..Moreover, the proposed research will have immediate economic impact by creating 1 postdoctoral position and retaining a graduate student and covering efforts of two key existing scientists. ..

..The information made available via these studies will be useful in developing new strategies for cancer prevention and treatment. ..