Table 1.
Identified NLSs and nuclear import pathways of Herpesviral DNA replicating enzymes. The NLSs identified so far for each herpesviral DNA replication proteins are indicated, as well as the IMPs binding them. The subcellular localization of each protein when individually expressed is also indicated (loc. alone). Additional details are reported in respect to the nuclear import pathways of DNA polymerase and helicase/primase holoenzymes. Pol, DNA polymerase catalytic subunit; PAP, DNA polymerase processivity factor: hNLS, hydrophobic NLS; cNLS, classical NLS; bip, bipartite NLS; N, nucleus; C, cytoplasm; IMPs, importins.
| HSV-1 | HCMV | |||||||
|---|---|---|---|---|---|---|---|---|
| protein | name | NLS | IMPs | loc. alone | name | NLS | IMPs | loc. alone |
| processivity factor | UL42 | 1 cNLS bip [55] | a/β | N [55] | UL44 | 1 cNLS [52] | a/β | N [52] |
| DNA polymerase | UL30 | 1 cNLS bip [53] 1 NLS hyd [53,56] | a/β | N [53,56,87] | UL54 | 1 cNLS [54] 1 NLS hyd [56] | a/β | N [56] |
| primase | UL5 | C [63,64] | UL70 | C [52] | ||||
| helicase | UL52 | C [63,64] | UL105 | N in infected cells [110] | ||||
| primase-associated factor | UL8 | putative PY-NLS (see text for details) | C [63,64] | UL102 | ||||
| ssDNA binding protein | UL29 | ? | UL57 | |||||
| DNA polymerase holoenzyme nuclear import | Individual subunits and holoenzyme [55] | Individual subunits and holoenzyme [54] | ||||||
| PAP status | Monomer [76] | Dimer [77,106]; transported to the nucleus as dimer [105] | ||||||
| Helicase primase complex nuclear import | Transported as a trimeric complex C [63,64] | Not known, but UL70 can localize to the nucleus independently of the other subunits if the cellular chaperone DNAJB6-a is overexpressed [109] | ||||||
| EBV | KHSV | |||||||
| protein | name | NLS | IMPs | loc. alone | name | NLS | IMPs | loc. alone |
| processivity factor | BMRF1 | 1 cNLS [84] | N [84] | ORF59 | 1 cNLS [59] | N [59] | ||
| DNA polymerase | BALF5 | C [60] | ORF9 | C [59] | ||||
| primase | BSLF1 | C [61] | ORF44 | putative PY-NLS (see text for details) | C [59] | |||
| helicase | BBLF4 | C [61] | ORF56 | C [59] | ||||
| primase-associated factor | BBLF2/3 | C [61] | ORF40/41 | C [59] | ||||
| ssDNA binding protein | BALF2 | ORF6 | ||||||
| DNA polymerase holoenzyme nuclear import | Piggy back as mediated by PAP [60] | Piggy back as mediated by PAP [59] | ||||||
| PAP status | Multimer [78,114] | Dimer [79,115 ]; transported to the nucleus as dimer [116] | ||||||
| Helicase primase complex nuclear import | Imported as a complex; BBLF4 can be imported if expressed with the ZTA transactivator [ 61] | pol/PAP and all the helicase primase subunits need to be simultaneously expressed to achieve nuclear targeting [62] | ||||||