Fitting CRISPR-associated Cas3 into the helicase family tree.
Helicases utilize NTPs to modulate their binding to nucleic acids and many of these enzymes also unwind DNA or RNA duplexes in an NTP-dependent fashion. These proteins are phylogenetically related but functionally diverse, with essential roles in virtually all aspects of nucleic acid metabolism. A new class of helicases associated with RNA-guided adaptive immune systems in bacteria and archaea has recently been identified. Prokaryotes acquire resistance to invading genetic parasites by integrating short fragments of foreign nucleic acids into repetitive loci in the host chromosome known as CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR-associated gene 3 (cas3) encodes a conserved helicase protein that is essential for phage defense. Here we review recent advances in Cas3 biology, and provide a new phylogenetic framework that positions Cas3 in the helicase family tree. We anticipate that this Cas3 phylogeny will guide future biochemical and structural studies.
Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59718, United States.
Ryan N
RN
Jackson
Department of Plant Sciences and Plant Pathology, Montana State University, Bozeman, MT 59718, United States.
Matthew
M
Lavin
Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59718, United States.
Joshua
J
Carter
Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59718, United States. Electronic address: bwiedenheft@gmail.com.
Blake
B
Wiedenheft
D000595:Amino Acid Sequence; D001105:Archaea / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D001419:Bacteria / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D064130:CRISPR-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment
D064130:CRISPR-Associated Proteins; D004265:DNA Helicases