| First Author | Weiss RS | Year | 2003 |
| Journal | Mol Cell Biol | Volume | 23 |
| Issue | 3 | Pages | 791-803 |
| PubMed ID | 12529385 | Mgi Jnum | J:81636 |
| Mgi Id | MGI:2449744 | Doi | 10.1128/MCB.23.3.791-803.2003 |
| Citation | Weiss RS, et al. (2003) Critical role for mouse Hus1 in an S-phase DNA damage cell cycle checkpoint. Mol Cell Biol 23(3):791-803 |
| abstractText | Mouse Hus1 encodes an evolutionarily conserved DNA damage response protein. In this study we examined how targeted deletion of Hus1 affects cell cycle checkpoint responses to genotoxic stress. Unlike hus1(-) fission yeast (Schizosaccharomyces pombe) cells, which are defective for the G(2)/M DNA damage checkpoint, Hus1-null mouse cells did not inappropriately enter mitosis following genotoxin treatment. However, Hus1-deficient cells displayed a striking S-phase DNA damage checkpoint defect. Whereas wild-type cells transiently repressed DNA replication in response to benzo(a)pyrene dihydrodiol epoxide (BPDE), a genotoxin that causes bulky DNA adducts, Hus1-null cells maintained relatively high levels of DNA synthesis following treatment with this agent. However, when treated with DNA strand break-inducing agents such as ionizing radiation (IR), Hus1-deficient cells showed intact S-phase checkpoint responses. Conversely, checkpoint-mediated inhibition of DNA synthesis in response to BPDE did not require NBS1, a component of the IR-responsive S-phase checkpoint pathway. Taken together, these results demonstrate that Hus1 is required specifically for one of two separable mammalian checkpoint pathways that respond to distinct forms of genome damage during S phase. |
