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Table 1 Experimentally characterized and predicted functions of the core components of CRISPR-Cas systems

From: Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems

Family

Experimental/in silicoevidence

Prediction

Cas1

Metal-dependent deoxyribonuclease; a unique fold consisting of a N-terminal β strand domain and a C-terminal α-helical domain [21, 68]; also binds RNA [21, 68]

Involved in integration of spacer DNA into CRISPR repeats.

Cas2

RNAse specific to U-rich regions [23]

Facilitates spacer selection and/or integration. Could be involved in further crRNA cleavage.

Cas3

(helicase and HD domain)

Single-stranded DNA nuclease (HD domain) and ATP-dependent helicase [24]; required for interference [13].

Cuts DNA during interference; promotes strand separation.

Stand alone HD nuclease

Metal-dependent deoxyribonuclease specific for double-stranded oligonucleotides [69].

Cuts DNA during interference.

Cas4

RecB-like nuclease homolog with three-cysteine C-terminal cluster [5]

Might be involved in spacer acquisition

Cas5

RAMP [5], subunit of Cascade complex [8, 13].

Might substitute for Cas6 if catalytically active. Otherwise might be involved in both interference and adaptation stages.

Cas6

RAMP [5]; metal-independent endoribonuclease that generates crRNAs, subunit of Cascade complex [8, 13–15, 17].

 

Cas7

RAMP [5], subunit of Cascade complex [13]; present Cascade complex of I-E systems in 6 copies [8] and in several copies in I-A systems [16].

Implicated in interference; binds crRNA; if enzymatically active, might be involved in RNA-guided RNA cleavage.

Cas8

(large subunit)

Subunit of Cascade complex [13].

Inactivated Cas10 polymerase-like protein, binds DNA, interacts with HD domain and a RAMP carrying crRNA; could be involved in both interference and spacer selection stages.

Cas10

(large subunit, CRISPR polymerase)

Subunit of Cascade (Cmr) complex [15]; homologous to Palm domain polymerases and cyclases.

Same as Cas8, but fused to HD and thus cuts ssDNA; might be involved in strand separation.

Small subunit

Small, mostly alpha helical protein, subunit of Cascade complex [13, 15]; present in Cascade complex of I-E systems in two copies [8]

Specifically binds DNA; might recognize PAM.