TY - JOUR
T1 - Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage
AU - Avni, Dror
AU - Yang, Hong
AU - Martelli, Fabio
AU - Hofmann, Francesco
AU - ElShamy, Wael M.
AU - Ganesan, Shridar
AU - Scully, Ralph
AU - Livingston, David M.
N1 - Funding Information:
This work was supported by grants from the NCI, by a fellowship from the Lady Tata Memorial Trust (to D.A.), and by funds from the Sharf-Green Fund of the Dana-Farber Cancer Institute. We thank Drs. Cynthia C. Morton and Elizabeth P. Braverman of the Cytogenetics Core of the Dana-Farber/Harvard Cancer Center for their invaluable help in the development of FISH assays and Drs. Brian Dynlacht and Nick Dyson and members of the Livingston laboratory for many helpful conversations.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0141861977&partnerID=8YFLogxK
U2 - 10.1016/S1097-2765(03)00355-1
DO - 10.1016/S1097-2765(03)00355-1
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C2 - 14527418
AN - SCOPUS:0141861977
SN - 1097-2765
VL - 12
SP - 735
EP - 746
JO - Molecular Cell
JF - Molecular Cell
IS - 3
ER -
