Department of Normal and Pathological Histology and Cytology, University of Seville School of Medicine, Spain.
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Spain.
FEBS Open Bio. 2021 Mar;11(3):622-632. doi: 10.1002/2211-5463.13071. Epub 2021 Feb 20.
The repair of DNA breaks takes place in the context of chromatin and thus involves the activity of chromatin remodelers. The nucleosome acetyltransferase of H4 (NuA4) remodeler complex enables DNA break repair by relaxing flanking chromatin. Here, we show that MRG domain binding protein (MRGBP), a member of this complex, acts as a general inhibitor of DNA double-strand break repair. Upon its downregulation, repair is generally increased. This is particularly evident for the stimulation of early events of homologous recombination. Thus, MRGBP has an opposing role to the main catalytic subunits of the NuA4 complex. Our data suggest that MRGBP acts by limiting the activity of this complex in DNA repair, specifically by narrowing the extent of DNA-end resection.
DNA 断裂的修复发生在染色质的背景下，因此涉及染色质重塑剂的活性。H4 的核小体乙酰转移酶（NuA4）重塑复合物通过放松侧翼染色质来促进 DNA 断裂修复。在这里，我们表明，该复合物的成员 MRG 结构域结合蛋白（MRGBP）作为 DNA 双链断裂修复的通用抑制剂发挥作用。下调后，修复通常会增加。同源重组早期事件的刺激尤其明显。因此，MRGBP 与 NuA4 复合物的主要催化亚基作用相反。我们的数据表明，MRGBP 通过限制该复合物在 DNA 修复中的活性来发挥作用，特别是通过缩小 DNA 末端切除的程度。
