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Investigation on the formation, conversion and bioactivity of a G-quadruplex structure in the PALB2 gene
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文摘
There is a putative G-quadruplex sequence (PGS), 5′-G3ACAG4TTG2TG4 TAG4CAG2TTG3-3′, in the promoter region of the PALB2 gene. According to the importance of PALB2 in the process of homologous recombination and breast cancer, and the hypothesis that G-quadruplexes might play a role in transcriptional regulation, we evaluated the formation of G-quadruplex from this complex sequence, as well as its structural information and importance for PALB2 transcription. The G-rich sequence was suggested to form G-quadruplex structure in the NH4OAc solution with 3NH4+ ion by ESI-MS spectrometry, and it was testified in the KCl solution by CD experiments which showed the typical 290 nm band and a high melting temperature. We also classified the guanines in the sequence into four types and demonstrated their roles in the formation of the G-quadruplex structure. In addition, a luciferase assay proved that the formation of the G-quadruplex down-regulate the transcription of the gene. Therefore, our findings provided a foundation for the formation and bioactivity of the G-quadruplex in the promoter region of PALB2 gene and a novel insight for understanding PALB2 gene regulation.

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