Pellicioli A, Lee S E, Lucca C, Foiani M, Haber J E
Istituto F.I.R.C. di Oncologia Molecolare and, Dipartimento di Genetica e di Biologia dei, Microrganismi, Universita' degli Studi di Milano, 20133, Milan, Italy.
Mol Cell. 2001 Feb;7(2):293-300. doi: 10.1016/s1097-2765(01)00177-0.
Saccharomyces cells with one unrepaired double-strand break (DSB) adapt after checkpoint-mediated G2/M arrest. Adaptation is accompanied by loss of Rad53p checkpoint kinase activity and Chk1p phosphorylation. Rad53p kinase remains elevated in yku70delta and cdc5-ad cells that fail to adapt. Permanent G2/M arrest in cells with increased single-stranded DNA is suppressed by the rfa1-t11 mutation, but this RPA mutation does not suppress permanent arrest in cdc5-ad cells. Checkpoint kinase activation and inactivation can be followed in G2-arrested cells, but there is no kinase activation in G1-arrested cells. We conclude that activation of the checkpoint kinases in response to a single DNA break is cell cycle regulated and that adaptation is an active process by which these kinases are inactivated.
带有一个未修复双链断裂（DSB）的酿酒酵母细胞在检查点介导的G2/M期停滞之后会发生适应。适应过程伴随着Rad53p检查点激酶活性的丧失和Chk1p磷酸化。在未能适应的yku70delta和cdc5 - ad细胞中，Rad53p激酶水平仍然升高。单链DNA增加的细胞中的永久性G2/M期停滞可被rfa1 - t11突变抑制，但这种RPA突变不能抑制cdc5 - ad细胞中的永久性停滞。在G2期停滞的细胞中可以追踪检查点激酶的激活和失活，但在G1期停滞的细胞中没有激酶激活。我们得出结论，响应单个DNA断裂时检查点激酶的激活是受细胞周期调控的，并且适应是这些激酶失活的一个活跃过程。
