Imperial College London
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DrAlexisBarr

Faculty of Medicine, Institute of Clinical Sciences

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 7772a.barr Website

 
 
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Location

 

Office 6.12BLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Barr:2017:10.1038/ncomms14728,
author = {Barr, AR and Cooper, S and Heldt, FS and Butera, F and Stoy, H and Mansfeld, J and Novak, B and Bakal, C},
doi = {10.1038/ncomms14728},
journal = {Nature Communications},
pages = {1--17},
title = {DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression},
url = {http://dx.doi.org/10.1038/ncomms14728},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability.
AU  - Barr,AR
AU  - Cooper,S
AU  - Heldt,FS
AU  - Butera,F
AU  - Stoy,H
AU  - Mansfeld,J
AU  - Novak,B
AU  - Bakal,C
DO  - 10.1038/ncomms14728
EP  - 17
PY  - 2017///
SN  - 2041-1723
SP  - 1
TI  - DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/ncomms14728
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000396666700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/ncomms14728
UR  - http://hdl.handle.net/10044/1/63263
VL  - 8
ER  -
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