Table 4.
Genetic alterations conferring hypersensitivity to Top1 poisoning in fission yeast:
| Yeast Saccharomyces Pombe |
Humans
|
|||||
|---|---|---|---|---|---|---|
| Gene | Effect | Refs. | Function | Gene | Effect | Refs. |
| Rhp54 | HS | [129] | Homologous recombination (HR) | RAD52 | ? | |
| Rhp55 | LS | [129] | Homologous recombination (HR) | XRCC2 | HS | [219, 230, 234] |
| Rhp22A | LS | [129] | Homologous recombination (HR) | XRCC3 | HS | [219] |
| Rhp51 | S | [129] | RecA homolog; Rad52 epistasis G. | RAD51C | HS | [223] |
| rad22 | HS | [248] | Rec A homolog; functions with Mus81 | |||
|
| ||||||
| Rad50 | HS | [129] | MRX/N complex; scaffold | RAD50 | ? | |
| Mus81 | S | [129] | 3′-flap endonuclease with Eme1; meiotic recombination | MUS81 | NS | [137] |
| Eme1 | S | [129] | Partner for mus81 nuclease | MUS81 | ? | |
| RusA | RSa | [129] | HJ resolvase | |||
|
| ||||||
| Pnk1 | Sb | [112] | Polynucleotide kinase phosphatase | PNKP | HS | [115] |
|
| ||||||
| Rqh1 | MS | [98] | Top3-associated helicase | WRN | HS | [227–229] |
| BLM | HS | [82] | ||||
|
| ||||||
| Crb2 | S | [249] | Adaptor for checkpoint kinases and checkpoint proteins | 53BP1 | ? | |
| BRCA1 | HS | [216] | ||||
|
| ||||||
| Chk1 | S | [155, 249, 250] | Checkpoint effector kinase | CHK1 | S | [162, 165] |
|
| ||||||
| Swi1 | HS | [251] | Mating-type switching | TIMELESS | ||
Abbreviations for effect: HS, S, MS, and CS correspond to hypersensitivity, sensitivity, moderate sensitivity, and conditional sensitivity to camptothecin, respectively. NS: no hypersensitivity.
rusA suppresses hypersensitivity of Mus81/Eme1− but does not reverse sensitivity of rqh1−; rusA also suppresses the lethality of double mutants for Mus81/Eme1 + rqh1 [129]. RusA expressed in budding yeast partially suppresses hypersensitivity to CPT in Mms4-deficient cells [126].
Pnk1- cells are hypersensitive to CPT in the absence of additional defects, indicating difference from budding (see [a]) and importance of this pathway in fission yeast, which like mammals possesses a gene that has both 3′-phosphatase and 5′-kinase activity [112].