Thursday, July 17, 2025 7/17/2025

Regulation and Localization of Mismatch Repair Proteins

Award Number: R16GM146801
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: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2026

Group Awards By:

View Award Description

Regulation and Localization of Mismatch Repair Proteins - Principal Investigator/Program Director (Last, first, middle): Haye, Joanna, Elizabeth Abstract: DNA mismatch repair (MMR) is a highly conserved process. A functional MMR pathway is essential for maintaining genome integrity; loss of MMR results in genome instability and cancer in higher eukaryotes. For example, defects in MMR genes result in Lynch Syndrome, a common hereditary cancer syndrome resulting in early onset cancers of the colon, endometrium, ovaries, small intestine, hepatobiliary tract, upper urinary tract as well as other tissues. In our most recent publication, we showed that in yeast, deletion of Modulator of Transcription (also known as Not4) or General Control Nonderepressible 5 (Gcn5) modulate the levels of Msh2, a major MMR component. Loss of Gcn5 significantly decreases Msh2, whereas deleting Not4 stabilizes functional Msh2. Not4 and Gcn5 are proteins that ubiquitylate and acetylate various proteins respectively. We hypothesize that Not4 and Gcn5 modify yeast MutSα (comprised of Ms2 and Msh6) and that the modifications affect the stability of the complex. Using the yeast Saccharomyces cerevisiae (S. cerevisiae), the first aim of the proposed research is to establish the role of Gcn5 and Not4 in the regulation of the major mismatch recognition complex MutSα. Our previous experiments have also shown that yeast MutS tracks with the replication machinery during DNA replication. Human MutSα is recruited to chromatin through specific histone modifications and interacts with the replication machinery by binding PCNA, the DNA polymerase processivity factor. However, the modifications that recruit human MutSα are not utilized in yeast. How yeast MutSα is recruited to chromatin remains elusive. The second aim of this research is to determine the role of post- translational modifications in MutSα recruitment to chromatin. PHS398 (Rev. 5/01) Page Continuation Format Page


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 = $187,500 )
2025	2025	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	4	4/29/2025	NON-COMPETING CONTINUATION	$187,500
														Subtotal = $187,500

Issue Date FY: 2024 ( Subtotal = $187,500 )
2024	2024	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	3	5/15/2024	NON-COMPETING CONTINUATION	$187,500
														Subtotal = $187,500

Issue Date FY: 2023 ( Subtotal = $240,500 )
2023	2023	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	001	2	6/26/2023	SUPPLEMENT FOR EXPANSION	$53,000
2023	2023	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	2	5/25/2023	NON-COMPETING CONTINUATION	$187,500
														Subtotal = $240,500

Issue Date FY: 2022 ( Subtotal = $179,150 )
2022	2022	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	1	7/26/2022	NEW	$179,150
														Subtotal = $179,150

Grand Total All Awards = $794,650

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation and Localization of Mismatch Repair Proteins

Award Number: R16GM146801

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: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer