Iyer Lakshminarayan M, Babu M Madan, Aravind L
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
Cell Cycle. 2006 Apr;5(7):775-82. doi: 10.4161/cc.5.7.2629. Epub 2006 Apr 1.
Aided by sensitive sequence profile searches we identify a novel conserved domain in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p (hence HIP116, Rad5p N-terminal domain: HIRAN domain). We show that the HIRAN domain is found as a standalone protein in several bacteria and prophages, or fused to other catalytic domains, such as a nuclease of the restriction endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes. Based on a network of contextual connections in the form of domain architectures, conserved gene neighborhoods and functional interactions we predict that the HIRAN domain is likely to function as a DNA-binding domain that probably recognizes features associated with damaged DNA or stalled replication forks. It might thus act as a sensor to initiate a damaged DNA checkpoint and engage different DNA repair and chromatin remodeling or modifying activities to these sites. In evolutionary terms, the fusion of the HIRAN domain, and the functionally analogous RAD18 Zn-finger and the PARP-type Zn-finger to SWI2/SNF2 ATPases appears to have been a notable factor for recruiting these ATPases for chromatin modification and remodeling in the context of DNA repair.
在敏感的序列谱搜索的辅助下，我们在以HIP116和Rad5p为代表的SWI2/SNF2蛋白的N端区域鉴定出一个新的保守结构域（因此称为HIP116、Rad5p N端结构域：HIRAN结构域）。我们发现，HIRAN结构域在几种细菌和原噬菌体中作为独立蛋白存在，或者在真核生物中与其他催化结构域融合，如限制内切酶折叠的核酸酶和TDP1样DNA磷酸二酯酶。基于以结构域结构、保守基因邻域和功能相互作用形式存在的上下文连接网络，我们预测HIRAN结构域可能作为DNA结合结构域发挥作用，可能识别与受损DNA或停滞的复制叉相关的特征。因此，它可能作为一种传感器启动受损DNA检查点，并在这些位点参与不同的DNA修复以及染色质重塑或修饰活动。从进化角度来看，HIRAN结构域以及功能类似的RAD18锌指和PARP型锌指与SWI2/SNF2 ATP酶的融合，似乎是在DNA修复背景下招募这些ATP酶进行染色质修饰和重塑的一个重要因素。
