Avni Dror, Yang Hong, Martelli Fabio, Hofmann Francesco, ElShamy Wael M, Ganesan Shridar, Scully Ralph, Livingston David M
Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Mol Cell. 2003 Sep;12(3):735-46. doi: 10.1016/s1097-2765(03)00355-1.
The Rb protein suppresses development of an abnormal state of endoreduplication arising after S phase DNA damage. In diploid, S phase cells, the activity of protein phosphatase 2A (PP2A) licenses the stable association of un(der)phosphorylated Rb with chromatin. After damage, chromatin-associated pRb is attracted to certain chromosomal replication initiation sites in the order in which they normally fire. Like S phase DNA damage in Rb(-/-) cells, specific interruption of PP2A function in irradiated, S phase wt cells also elicited a state of endoreduplication. Thus, PP2A normally licenses the recruitment of Rb to chromatin sites in S phase from which, after DNA damage, it relocalizes to selected replication control sites and suppresses abnormal, postdamage rereplicative activity.
Rb蛋白可抑制S期DNA损伤后出现的内复制异常状态的发展。在二倍体S期细胞中，蛋白磷酸酶2A（PP2A）的活性使未（经）磷酸化的Rb与染色质稳定结合。损伤后，与染色质相关的pRb按其正常激活顺序被吸引到某些染色体复制起始位点。与Rb（-/-）细胞中的S期DNA损伤一样，在受辐射的S期野生型细胞中PP2A功能的特异性中断也引发了内复制状态。因此，PP2A通常使Rb在S期被募集到染色质位点，DNA损伤后，Rb从这些位点重新定位到选定的复制控制位点，并抑制损伤后异常的再复制活性。
