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Telomere structure and function in Arabidopsis

Award Number: R01GM065383
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2002
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Telomere structure and function in Arabidopsis - Project Summary: Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism. Environmental assaults can dramatically elevate ROS, overwhelming the defenses of cellular antioxidants, and triggering damage to essential macromolecules particularly DNA. Oxidative damage is linked to numerous disease states, but despite much research, fundamental questions remain on how cells avert the detrimental impacts of ROS. Mounting evidence implicates telomere proteins in functions beyond the chromosome terminus. Both Protection of Telomeres 1 (POT1) and the telomerase catalytic subunit TERT traffic in and out of the nucleus and are implicated in various aspects of the response to oxidative damage in mammalian cells. However, unmasking potential non-telomeric functions is problematic because of their critical roles in telomere maintenance and stability. In this renewal application, the model eukaryote Arabidopsis thaliana is employed to study how telomere-associated proteins (TAPs) respond to and mitigate oxidative stress. Arabidopsis encodes two highly divergent POT1 paralogs, AtPOT1a and AtPOT1b, which exhibit separation-of-function with respect to canonical telomere biology, and hence present a unique opportunity to elucidate the full complement of POT1 functions. The proposal builds on additional preliminary showing that AtPOT1b accumulates in the cytoplasm, and loss of AtPOT1b significantly elevates ROS and activates numerous cellular defenses against oxidative stress. AtTERT carries a mitochondrial localization signal, suggesting that it too may regulate the response to ROS. The central hypothesis of this proposal is that the TAPs, AtPOT1a, AtPOT1b and AtTERT, serve important roles in the cellular defense against oxidative damage. This hypothesis will be examined through two Specific Aims. For Aim 1, the breadth of POT1 functions in promoting genome integrity will be assessed by testing how POT1a and POT1b regulate oxidative damage in telomeric and non-telomeric DNA, and how POT1b cooperates with POT1a and TERT to avert genome destabilization. The role of ATR signaling in reproductive progenitor cells will be examined in pot1b mutants. Finally, the evolutionary origin of stress response functions in POT1 proteins will be explored. In Aim 2, three complementary strategies will probe the molecular mechanism and interaction partners of TAPs in non-telomeric pathways. These include monitoring the subcellular trafficking of TAPs in response to stress, quantitative mass spec to identify protein binding partners and stress-induced post-translational modifications, and a novel suppressor screen to explore the genetic pathway that enables POT1b and TERT to promote plant development. These studies will increase understanding of the cross- talk between TAPs and the stress response, open new horizons for exploring the non-canonical functions of POT1, and provide a roadmap to explore rare splice variants of human POT1 that cannot associate with telomeres, and yet are associated with increased predisposition to cancer.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$39,590 )
2026	2023	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	20	3/26/2026	NON-COMPETING CONTINUATION	-$39,590
														Subtotal = -$39,590

Issue Date FY: 2023 ( Subtotal = $378,750 )
2023	2023	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	20	7/25/2023	NON-COMPETING CONTINUATION	$378,750
														Subtotal = $378,750

Issue Date FY: 2022 ( Subtotal = $378,750 )
2022	2022	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	19	7/11/2022	NON-COMPETING CONTINUATION	$378,750
														Subtotal = $378,750

Issue Date FY: 2021 ( Subtotal = $378,750 )
2021	2021	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	002	18	7/22/2021	NON-COMPETING CONTINUATION	$378,750
2021	2020	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	17	7/2/2021	COMPETING CONTINUATION	$58,450
2021	2018	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	16	7/2/2021	NON-COMPETING CONTINUATION	-$58,450
														Subtotal = $378,750

Issue Date FY: 2020 ( Subtotal = $378,750 )
2020	2020	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	002	17	8/11/2020	COMPETING CONTINUATION	$378,750
2020	2018	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	16	8/3/2020	NON-COMPETING CONTINUATION	$0
2020	2018	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	16	4/22/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $378,750

Issue Date FY: 2018 ( Subtotal = $372,775 )
2018	2018	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	16	4/27/2018	NON-COMPETING CONTINUATION	$360,668
2018	2018	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	15	12/20/2017	SUPPLEMENT FOR EXPANSION	$12,107
														Subtotal = $372,775

Issue Date FY: 2017 ( Subtotal = $360,668 )
2017	2017	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	15	6/20/2017	NON-COMPETING CONTINUATION	$36,067
2017	2017	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	15	4/26/2017	NON-COMPETING CONTINUATION	$324,601
														Subtotal = $360,668

Issue Date FY: 2016 ( Subtotal = $357,971 )
2016	2016	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	14	5/12/2016	NON-COMPETING CONTINUATION	$357,971
														Subtotal = $357,971

Issue Date FY: 2015 ( Subtotal = $352,483 )
2015	2015	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	13	5/13/2015	COMPETING CONTINUATION	$352,483
2015	2014	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	12	5/8/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $352,483

Issue Date FY: 2014 ( Subtotal = $333,449 )
2014	2014	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	12	3/18/2014	NON-COMPETING CONTINUATION	$33,345
2014	2014	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	12	11/27/2013	NON-COMPETING CONTINUATION	$300,104
														Subtotal = $333,449

Issue Date FY: 2013 ( Subtotal = $321,778 )
2013	2013	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	11	11/28/2012	NON-COMPETING CONTINUATION	$300,104
2013	2013	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	11	6/21/2013	NON-COMPETING CONTINUATION	$21,674
														Subtotal = $321,778

Issue Date FY: 2012 ( Subtotal = $333,449 )
2012	2012	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	10	11/29/2011	NON-COMPETING CONTINUATION	$300,104
2012	2012	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	10	2/27/2012	NON-COMPETING CONTINUATION	$33,345
														Subtotal = $333,449

Issue Date FY: 2011 ( Subtotal = $328,204 )
2011	2011	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	9	12/17/2010	COMPETING CONTINUATION	$328,204
2011	2009	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	8	12/16/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $328,204

Issue Date FY: 2009 ( Subtotal = $512,380 )
2009	2009	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Trans-NIH Recovery Act Research Support	001	8	9/15/2009	SUPPLEMENT FOR EXPANSION	$227,785
2009	2009	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	8	4/10/2009	NON-COMPETING CONTINUATION	$284,595
														Subtotal = $512,380

Issue Date FY: 2008 ( Subtotal = $284,595 )
2008	2008	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	7	4/9/2008	NON-COMPETING CONTINUATION	$284,595
														Subtotal = $284,595

Issue Date FY: 2007 ( Subtotal = $284,595 )
2007	2007	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	6	4/12/2007	NON-COMPETING CONTINUATION	$284,595
														Subtotal = $284,595

Issue Date FY: 2006 ( Subtotal = $287,839 )
2006	2006	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	5	4/20/2006	COMPETING CONTINUATION	$287,839
														Subtotal = $287,839

Issue Date FY: 2005 ( Subtotal = $274,995 )
2005	2005	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	4	4/18/2005	NON-COMPETING CONTINUATION	$274,995
														Subtotal = $274,995

Issue Date FY: 2004 ( Subtotal = $274,995 )
2004	2004	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	3	3/12/2004	NON-COMPETING CONTINUATION	$274,995
														Subtotal = $274,995

Grand Total All Awards = $6,715,717

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Telomere structure and function in Arabidopsis

Award Number: R01GM065383

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2002

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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