The HIRAN domain and recruitment of chromatin remodeling and repair activities to damaged DNA.
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.
Iyer
Lakshminarayan M
LM
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
Babu
M Madan
MM
Aravind
L
L
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D030562:Databases, Protein; D005057:Eukaryotic Cells / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry*
D002868:Chromosomal Proteins, Non-Histone; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors