Author/Authors :
Wang، نويسنده , , Rui-Hong and Sengupta، نويسنده , , Kundan and Li، نويسنده , , Cuiling and Kim، نويسنده , , Hyun-Seok and Cao، نويسنده , , Liu and Xiao، نويسنده , , Cuiying and Kim، نويسنده , , Sangsoo and Xu، نويسنده , , Xiaoling and Zheng، نويسنده , , Yin and Chilton، نويسنده , , Beverly and Jia، نويسنده , , Rong and Zheng، نويسنده , , Zhi-Ming and Appella، نويسنده , , Ettore and Wang، نويسنده , , Xin Wei and Ried، نويسنده , , Thomas and Deng، نويسنده , , Chu-Xia، نويسنده ,
Abstract :
Summary
er eukaryotes, Sir2 serves as a histone deacetylase and is implicated in chromatin silencing, longevity, and genome stability. Here we mutated the Sirt1 gene, a homolog of yeast Sir2, in mice to study its function. We show that a majority of SIRT1 null embryos die between E9.5 and E14.5, displaying altered histone modification, impaired DNA damage response, and reduced ability to repair DNA damage. We demonstrate that Sirt1+/−;p53+/− mice develop tumors in multiple tissues, whereas activation of SIRT1 by resveratrol treatment reduces tumorigenesis. Finally, we show that many human cancers exhibit reduced levels of SIRT1 compared to normal controls. Thus, SIRT1 may act as a tumor suppressor through its role in DNA damage response and genome integrity.
