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Single-molecule Visualization and Mechanisms of DNA Recombination and Intersecting DNA Transactions

Award Number: R35GM131900
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: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Single-molecule Visualization and Mechanisms of DNA Recombination and Intersecting DNA Transactions - Project Description The broad objective of this proposal is to understand the mechanism of homologous recombination and its relationship to chromosome maintenance in both Bacteria and Eukarya. Our approach is to reconstitute increasingly more complex reactions that recapitulate the steps of the homologous recombination process, using purified proteins from Escherichia coli and from Saccharomyces cerevisiae, and to use sophisticated biochemical and biophysical methods of analysis. In particular, we will use single-molecule visualization to image key steps and intermediates of these complex biological processes. We have developed new experimental strategies for studying protein-DNA interactions at the single-molecule level. We devised several approaches wherein we can easily manipulate an individual DNA molecule and expose it to a variety of different proteins, enzymes, and buffers. Using fluorescent detection, we can image individual proteins on DNA or detect their action on individual DNA molecules, typically in real-time. We propose to continue to use these approaches to study unresolved aspects of recombinational DNA repair and its interface with the important biological processes of chromatin remodeling and DNA replication. We seek to continue to address unresolved questions regarding the dynamic behavior of RecA/Rad51 nucleoprotein filaments and their regulation by protein mediators and modulators; the mechanism by which RecA and Rad51 find DNA sequence homology; the reconstitution increasingly more complex recombination processes using purified proteins; the mechanism and function of DNA helicases and their partner proteins; and understanding the mechanism of DNA transactions that intersect with recombination, namely, chromatin remodeling and DNA replication.


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 = $763,333 )
2026	2026	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	8	1/29/2026	NON-COMPETING CONTINUATION	$763,333
														Subtotal = $763,333

Issue Date FY: 2025 ( Subtotal = $848,148 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	002	7	4/15/2025	NON-COMPETING CONTINUATION	$848,148
2025	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	6	11/21/2024	COMPETING CONTINUATION	$0
2025	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	5	4/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $848,148

Issue Date FY: 2024 ( Subtotal = $846,711 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	002	6	4/17/2024	COMPETING CONTINUATION	-$1,437
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	6	3/28/2024	COMPETING CONTINUATION	$848,148
2024	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	5	3/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $846,711

Issue Date FY: 2023 ( Subtotal = $802,492 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	5	3/16/2023	NON-COMPETING CONTINUATION	$802,492
														Subtotal = $802,492

Issue Date FY: 2022 ( Subtotal = $802,492 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	4	3/22/2022	NON-COMPETING CONTINUATION	$722,240
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	4	7/22/2022	NON-COMPETING CONTINUATION	$80,252
														Subtotal = $802,492

Issue Date FY: 2021 ( Subtotal = $813,982 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	3	3/17/2021	NON-COMPETING CONTINUATION	$813,982
														Subtotal = $813,982

Issue Date FY: 2020 ( Subtotal = $903,186 )
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	2	6/18/2020	SUPPLEMENT FOR EXPANSION	$91,606
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	2	3/16/2020	NON-COMPETING CONTINUATION	$811,580
														Subtotal = $903,186

Issue Date FY: 2019 ( Subtotal = $746,558 )
2019	2019	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	1	3/26/2019	NEW	$746,558
														Subtotal = $746,558

Grand Total All Awards = $6,526,902

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Single-molecule Visualization and Mechanisms of DNA Recombination and Intersecting DNA Transactions

Award Number: R35GM131900

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: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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