Invasive DNA, chopped and in the CRISPR

Abstract

In this issue of Structure, Wiedenheft et al. describe the structure and activity of Cas1, the only protein associated with all CRISPR loci. Cas1 is a metal-dependent deoxyribonuclease, consistent with a role in the adaptation phase of CRISPR immunity against invading nucleic acids.

Figure 1. Possible Roles for Cas1 in CRISPR Immunity

CRISPR loci include a set of repeats (white boxes) separated by spacers (colored boxes) with sequences that match phage and plasmid DNA that often invade bacteria. These clusters are preceded by a “leader” sequence and are usually flanked by cas genes. When a phage that does not carry a sequence identical to any CRISPR spacers infects bacteria, most cells succumb to the infection. At a low frequency, however, a fragment of the phage DNA can become incorporated as a new repeat-spacer unit at one end of the CRISPR locus (top panel). Cas1 is a likely candidate in the adaptation process, and Weidenheft et al. (2009) demonstrate DNase activity of Cas1 consistent with this possibility. The new spacer sequence is then included among the crRNAs generated by the CRISPR locus, leading to immunity against subsequent infections by the phage (bottom panel).