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SET7 UHRF1 DNA Use for regulating DNA damage repair by SET7-mediated UHRF1 methylation

机译:SET7 UHRF1 DNA用于通过SET7介导的UHRF1甲基化调节DNA损伤修复

摘要

The present invention relates to the use of DNA damage repair control through SET7 mediated UHRF1 methylation. UHRF1 is a major epigenetic regulator of DNA methylation maintenance and heterochromatin formation, and the role of UHRF1 in DNA damage repair has been recently emphasized, but the mechanism of regulation of UHRF1 is still unclear. In the present invention, it was found that UHRF1 is methylated by SET7 and demethylated by LSD1. In addition, it was confirmed that methylation of UHRF1 was induced in response to DNA damage, and phosphorylation in S group was necessary for the interaction with SET7. In addition, UHRF1 methylation promoted the conjugation of polyubiquitin chains to PCNA and promoted homologous recombination for DNA repair. In addition, SET7-mediated UHRF1 methylation has been shown to be essential for cell viability against DNA damage. Accordingly, in the present invention, the mechanism of regulation according to the methylation status of UHRF1 by SET7 and LSD1 in the double-helix damage repair pathway was revealed.
机译:本发明涉及通过SET7介导的UHRF1甲基化的DNA损伤修复控制的用途。 UHRF1是DNA甲基化维持和异染色质形成的主要表观遗传调节剂,最近已强调了UHRF1在DNA损伤修复中的作用,但对UHRF1的调节机制尚不清楚。在本发明中,发现UHRF1被SET7甲基化并且被LSD1去甲基。另外,已经证实UHRF1的甲基化是响应DNA损伤而诱导的,并且S基团中的磷酸化对于与SET7的相互作用是必需的。此外,UHRF1甲基化促进了多泛素链与PCNA的结合,并促进了DNA修复的同源重组。此外,SET7介导的UHRF1甲基化已被证明对于抵抗DNA损伤的细胞生存力至关重要。因此,在本发明中,揭示了根据双螺旋损伤修复途径中SET7和LSD1对UHRF1的甲基化状态的调节机制。

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