Kang Keunsoo, Choi Yoonjung, Moon Hyeonjin, You Chaelin, Seo Minjin, Kwon Geunho, Yun Jahyun, Beck Boram, Kang Kyuho
Department of Microbiology, College of Science & Technology, Dankook University, Cheonan 31116, Korea.
Deargen Inc., 193, Munji-ro, Yuseong-gu, Daejeon 34051, Korea.
Cancers (Basel). 2021 May 22;13(11):2547. doi: 10.3390/cancers13112547.
RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound -regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated -regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated -regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins.
RAD51是一种在同源重组中起关键作用的重组酶。尽管RAD51在同源重组中的作用已得到广泛研究，但尚不清楚RAD51是否能作为辅助因子参与基因调控。在本研究中，我们发现证据表明，在GM12878、HepG2、K562和MCF-7细胞系中，RAD51可能与E-box蛋白（如USF1、USF2和/或MITF）共同参与自噬途径相关基因的调控。在所有四个细胞系中，在RAD51结合的调控元件处均显著鉴定出典型的USF结合基序（CACGTG）。此外，全基因组范围内的USF1、USF2和/或MITF结合区域与同一细胞系中RAD51相关的调控元件显著重合。有趣的是，在HepG2和MCF-7细胞系中，自噬途径相关基因（如ATG3和ATG5）的启动子被RAD51显著占据并受其调控。综上所述，这些结果揭示了RAD51的一种新作用，并提供了证据表明RAD51相关的调控元件可能与E-box结合蛋白一起参与调控自噬相关基因。
