Thursday, January 1, 2026 1/1/2026

Genome Maintenance via the BRCA-RAD54 Axis

Award Number: R01GM141091
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: 06/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Genome Maintenance via the BRCA-RAD54 Axis - ABSTRACT Homology-directed DNA repair (HDR) is a universal, conserved mechanism for the repair of DNA double- strand breaks and the maintenance of DNA replication forks. While HDR is relatively well understood in bacteria and lower eukaryotes, glaring knowledge gaps remain in the appreciation of mechanisms in mammals, because of greatly added complexity including myriad factors that are unique. Notably, several breast and ovarian tumor suppressors, including BRCA1-BARD1, BRCA2, and PALB2, have been implicated in HDR in mammals, and emerging evidence provides glimpses of the roles that they fulfill. However, a holistic understanding the molecular mechanisms of human HDR has been hampered by the immense challenge of expressing and purifying these very large proteins and protein complexes for mechanistic workup. My laboratory has overcome this challenge, allowing us to demonstrate the pivotal role of BRCA2 in complex with its obligatory partner DSS1 in facilitating the assembly of catalytically active filaments of the RAD51 recombinase on single-stranded DNA and to reveal a late role of the BRCA1-BARD1 complex in HDR via the promotion of RAD51-mediated DNA strand invasion. In this proposal, we aim to fill several knowledge gaps regarding how BRCA1-BARD1, BRCA2-DSS1, and PALB2 synergize in two distinct stages of the HDR process. Specifically, we will apply an integrated approach that encompasses reconstitution biochemistry, single-molecule biophysics, structural biology, DNA fiber analysis, and advanced cell biology to interrogate how the aforementioned tumor suppressors and their partner HDR factors, such as RAD54, help promote the assembly of the RAD51-ssDNA nucleoprotein filament and the catalysis of DNA strand invasion within the context of chromatin. The results from our work will bring molecular and mechanistic clarity to RAD51- dependent HDR and the preservation of stressed DNA replication forks in human cells.


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 = $0 )
2026	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	000	5	12/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $325,500 )
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	001	5	9/3/2025	NON-COMPETING CONTINUATION	$32,550
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	000	5	3/26/2025	NON-COMPETING CONTINUATION	$292,950
														Subtotal = $325,500

Issue Date FY: 2024 ( Subtotal = $347,616 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	002	4	7/23/2024	NON-COMPETING CONTINUATION	$32,550
2024	2024	UNI OF TX HEALTH SCIENCE CTR SAN ANT	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	000	4	2/13/2024	NON-COMPETING CONTINUATION	$292,950
2024	2024	UNI OF TX HEALTH SCIENCE CTR SAN ANT	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	001	4	2/14/2024	SUPPLEMENT FOR EXPANSION	$22,116
														Subtotal = $347,616

Issue Date FY: 2023 ( Subtotal = $391,850 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	000	3	2/10/2023	NON-COMPETING CONTINUATION	$325,500
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	001	3	2/13/2023	SUPPLEMENT FOR EXPANSION	$66,350
														Subtotal = $391,850

Issue Date FY: 2022 ( Subtotal = $369,734 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	000	2	2/21/2022	NON-COMPETING CONTINUATION	$292,950
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	001	2	7/22/2022	SUPPLEMENT FOR EXPANSION	$44,234
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	002	2	8/3/2022	NON-COMPETING CONTINUATION	$32,550
														Subtotal = $369,734

Issue Date FY: 2021 ( Subtotal = $324,975 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Biomedical Research and Research Training	000	1	5/24/2021	NEW	$324,975
														Subtotal = $324,975

Grand Total All Awards = $1,759,675

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Genome Maintenance via the BRCA-RAD54 Axis

Award Number: R01GM141091

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: 06/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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