STAT3 modulates the DNA damage response pathway
STAT3 modulates the DNA damage response pathway
The STAT3 transcription factor is well known to function as an anti-apoptotic factor, especially in numerous malignancies. Recently we showed that STAT3 is cytoprotective and that cells lacking STAT3 are more sensitive to oxidative stress. A key feature of oxidative stress involves activation of the DNA damage pathway. However, a role for STAT3 or its contribution in response to DNA damage has not been described. In the present study we show that cells lacking STAT3 are less efficient in repairing damaged DNA. Moreover, STAT3 deficient cells show reduced activity of the ATM-Chk2 and ATR-Chk1 pathways, both important pathways in sensing DNA damage. Finally we show that MDC1, a regulator of the ATM-Chk2 pathway and facilitator of the DNA damage response, is modulated by STAT3 at the transcriptional level. These findings demonstrate that STAT3 is necessary for efficient repair of damaged DNA, partly by modulating the ATM-Chk2 and ATR-Chk1 pathways.
atm, atr, chk1, chk2, dna damage, dna repair, stat3
506-514
Barry, Seán P.
be2c2533-9d53-4421-8acc-18c078e18452
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Scarabelli, Tiziano M.
ac96a777-880e-4e39-9884-f11a0978da35
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3
December 2010
Barry, Seán P.
be2c2533-9d53-4421-8acc-18c078e18452
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Scarabelli, Tiziano M.
ac96a777-880e-4e39-9884-f11a0978da35
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3
Barry, Seán P., Townsend, Paul A., Knight, Richard A., Scarabelli, Tiziano M., Latchman, David S. and Stephanou, Anastasis
(2010)
STAT3 modulates the DNA damage response pathway.
International Journal of Experimental Pathology, 91 (6), .
(doi:10.1111/j.1365-2613.2010.00734.x).
Abstract
The STAT3 transcription factor is well known to function as an anti-apoptotic factor, especially in numerous malignancies. Recently we showed that STAT3 is cytoprotective and that cells lacking STAT3 are more sensitive to oxidative stress. A key feature of oxidative stress involves activation of the DNA damage pathway. However, a role for STAT3 or its contribution in response to DNA damage has not been described. In the present study we show that cells lacking STAT3 are less efficient in repairing damaged DNA. Moreover, STAT3 deficient cells show reduced activity of the ATM-Chk2 and ATR-Chk1 pathways, both important pathways in sensing DNA damage. Finally we show that MDC1, a regulator of the ATM-Chk2 pathway and facilitator of the DNA damage response, is modulated by STAT3 at the transcriptional level. These findings demonstrate that STAT3 is necessary for efficient repair of damaged DNA, partly by modulating the ATM-Chk2 and ATR-Chk1 pathways.
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Accepted/In Press date: 27 August 2010
Published date: December 2010
Keywords:
atm, atr, chk1, chk2, dna damage, dna repair, stat3
Identifiers
Local EPrints ID: 163055
URI: http://eprints.soton.ac.uk/id/eprint/163055
ISSN: 0959-9673
PURE UUID: 6f1cf20a-03d9-4128-afc8-f183522b31cb
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Date deposited: 02 Sep 2010 13:48
Last modified: 14 Mar 2024 02:04
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Contributors
Author:
Seán P. Barry
Author:
Paul A. Townsend
Author:
Richard A. Knight
Author:
Tiziano M. Scarabelli
Author:
David S. Latchman
Author:
Anastasis Stephanou
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