MutL homologs in restriction-modification systems and the origin of eukaryotic MORC ATPases.
The provenance and biochemical roles of eukaryotic MORC proteins have remained poorly understood since the discovery of their prototype MORC1, which is required for meiotic nuclear division in animals. The MORC family contains a combination of a gyrase, histidine kinase, and MutL (GHKL) and S5 domains that together constitute a catalytically active ATPase module. We identify the prokaryotic MORCs and establish that the MORC family belongs to a larger radiation of several families of GHKL proteins (paraMORCs) in prokaryotes. Using contextual information from conserved gene neighborhoods we show that these proteins primarily function in restriction-modification systems, in conjunction with diverse superfamily II DNA helicases and endonucleases. The common ancestor of these GHKL proteins, MutL and topoisomerase ATPase modules appears to have catalyzed structural reorganization of protein complexes and concomitant DNA-superstructure manipulations along with fused or standalone nuclease domains. Furthermore, contextual associations of the prokaryotic MORCs and their relatives suggest that their eukaryotic counterparts are likely to carry out chromatin remodeling by DNA superstructure manipulation in response to epigenetic signals such as histone and DNA methylation.
Iyer
Lakshminarayan M
LM
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. lakshmin@mail.nih.gov
Abhiman
Saraswathi
S
Aravind
L
L
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology / Q000600:supply & distribution; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D015280:DNA Restriction-Modification Enzymes / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D005057:Eukaryotic Cells / Q000201:enzymology*; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D000070956:MutL Proteins; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
D001426:Bacterial Proteins; D015280:DNA Restriction-Modification Enzymes; D029968:Escherichia coli Proteins; C513310:MORC1 protein, human; C074770:MutL protein, E coli; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins