Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage

Dror Avni; Hong Yang; Fabio Martelli; Francesco Hofmann; Wael M. ElShamy; Shridar Ganesan; Ralph Scully; David M. Livingston

doi:10.1016/S1097-2765(03)00355-1

Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage

Dror Avni
, Hong Yang
, Fabio Martelli
, Francesco Hofmann
, Wael M. ElShamy
, Shridar Ganesan
, Ralph Scully
, David M. Livingston^*

^*Corresponding author for this work

Beth Israel Deaconess Medical Center
IRCCS Istituto Dermopatico dell'Immacolata - Roma
Novartis
Harvard University

Research output: Contribution to journal › Article › peer-review

103 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	735-746
Number of pages	12
Journal	Molecular Cell
Volume	12
Issue number	3
DOIs	https://doi.org/10.1016/S1097-2765(03)00355-1
State	Published - 1 Sep 2003
Externally published	Yes

Funding

Funders	Funder number
National Cancer Institute	K01CA079576
Dana-Farber Cancer Institute
Lady Tata Memorial Trust

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/S1097-2765(03)00355-1

Cite this

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title = "Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage",

abstract = "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.",

author = "Dror Avni and Hong Yang and Fabio Martelli and Francesco Hofmann and ElShamy, \{Wael M.\} and Shridar Ganesan and Ralph Scully and Livingston, \{David M.\}",

note = "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.",

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doi = "10.1016/S1097-2765(03)00355-1",

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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.

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JF - Molecular Cell

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ER -

Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage

Abstract

Funding

UN SDGs

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