探討SMYD3在同源重組中扮演的角色

Abstract

SMYD3在腫瘤形成中為常見的致癌基因。癌症中，過度表現的SMYD3與細胞增殖和較差的預後有關聯。在這篇研究中，我們發現SMYD3會調控DNA 修復。 在microarray 和ChIP-seq結果顯示SMYD3會活化MDC1、EXO1和RAD54B等與同源重組相關的基因表現。SMYD3的缺乏會使細胞對DNA損傷較敏感，而且同源重組的修復機制也會產生缺陷。在缺乏SMYD3的細胞中-H2A.X foci存在的時間延長，而 MDC1與BRCA1 foci的形成減少。而且，當SMYD3被抑制時，在MDC1、 EXO1和RAD54B啟動子處H3K4me3的量也會跟著減少。總結，我們發現SMYD3藉由調控 MDC1、 EXO1和 RAD54B的表現進而影響同源重組修復的能力。

SMYD3 emerges as a common oncogene in tumorigenesis, and overexpression of SMYD3 is linked to increased cell proliferation and poor prognosis in human cancers. Here we show that SMYD3 regulates DNA repair. ChIP-seq and microarray analyses demonstrate that SMYD3 binds and activates homologous recombination genes (MDC1, EXO1, and RAD54B) in MCF7 cells. SMYD3-depleted cells became hypersensitive to DNA damage and were defective in homologous recombination repair. Retention of -H2A.X foci and decrease of MDC1 and BRCA1 foci were observed in SMYD3 knockdown cells. Moreover, depletion of SMYD3 inhibited H3K4 trimethylation on MDC1, EXO1, and RAD54B promoter. Together, we discover a novel mechanism of SMYD3 in homologous recombination by regulating the expression of MDC1, EXO1, and RAD54B.