Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage.
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.
Avni
Dror
D
Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Yang
Hong
H
Martelli
Fabio
F
Hofmann
Francesco
F
ElShamy
Wael M
WM
Ganesan
Shridar
S
Scully
Ralph
R
Livingston
David M
DM
D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics* / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D009154:Mutation / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D054648:Protein Phosphatase 2; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D016196:S Phase / Q000235:genetics* / Q000528:radiation effects; D013601:T-Lymphocytes / Q000378:metabolism / Q000528:radiation effects
D002843:Chromatin; D016160:Retinoblastoma Protein; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2