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Chromosome structure, duplication and stability in yeast

Award Number: R35GM141641
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: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Chromosome structure, duplication and stability in yeast - Project Summary/Abstract Eukaryotic genome duplication requires that each chromosomal base pair is copied efficiently, accurately and only once per cell division, a monumental demand given the millions to billions of base pairs that comprise eukaryotic genomes and the countless cell divisions required to form and sustain organisms. Severe defects in DNA replication are incompatible with life. However, mild perturbations in this process, while still capable of supporting cell division, and which can be challenging to identify using biochemical approaches, can compromise development and health over the course of multiple cell divisions. Regulation of the first step, the initiation of DNA replication that occurs at chromosomal positions called origins, is particularly critical in eukaryotic cells because their chromosomes require multiple spatially and temporally distributed origins for accurate and efficient duplication. Perturbations in origin number or distribution can promote cancer, stem cell aging, or developmental disorders. While the origin-binding proteins and molecular steps that define an origin are known, the mechanisms that regulate chromosomal origin number and distribution are unclear. A challenge is that chromatin heterogeneity exists across chromosomes as an intrinsic part of genome functional organization. Thus, the origin-binding proteins must work sufficiently enough within distinct chromatin environments to achieve a level of origin distribution that balances the competing demands for cell proliferation and genome stability. Dr. Fox's lab addresses the gaps in understanding how native chromatin structures regulate origin function by combining rigorous genetics and genomics to reveal chromatin-mediated mechanisms that impinge on the structure and function of Saccharomyces cerevisiae (yeast) origins. Emphasis is placed on the first step of origin formation, the origin licensing reaction, which occurs in G1-phase of the cell cycle that precedes the S-phase where origins perform their actual function, unwinding of the parental DNA for new DNA synthesis. Accumulating evidence reveals that the licensing step is particularly relevant to both genome stability and cell-fate decisions, but there is a paucity of molecular mechanisms regarding how it is regulated in vivo to achieve chromosomal origin distribution. Evolutionary conservation of the origin-binding proteins and multiple features of chromatin allow the Fox laboratory to leverage the experimental strengths of yeast to define fundamental mechanisms by which chromatin and the origin-binding proteins collaborate to form and distribute origins over the genome.


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: 2025 ( Subtotal = $383,200 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	5	4/4/2025	NON-COMPETING CONTINUATION	$383,200
2025	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	4	11/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $383,200

Issue Date FY: 2024 ( Subtotal = $383,200 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	4	7/23/2024	NON-COMPETING CONTINUATION	$38,320
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	4	4/11/2024	NON-COMPETING CONTINUATION	$344,880
														Subtotal = $383,200

Issue Date FY: 2023 ( Subtotal = $463,518 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	002	3	9/14/2023	SUPPLEMENT FOR EXPANSION	$73,305
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	3	5/11/2023	SUPPLEMENT FOR EXPANSION	$7,013
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	3	4/27/2023	NON-COMPETING CONTINUATION	$383,200
														Subtotal = $463,518

Issue Date FY: 2022 ( Subtotal = $383,200 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	2	7/21/2022	NON-COMPETING CONTINUATION	$38,320
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	2	4/7/2022	NON-COMPETING CONTINUATION	$344,880
														Subtotal = $383,200

Issue Date FY: 2021 ( Subtotal = $551,262 )
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	1	8/2/2021	SUPPLEMENT FOR EXPANSION	$168,262
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	1	3/25/2021	NEW	$383,000
														Subtotal = $551,262

Grand Total All Awards = $2,164,380

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Chromosome structure, duplication and stability in yeast

Award Number: R35GM141641

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: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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