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Role of GCNA in preserving genome integrity and fertility

Award Number: R01GM127569
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: 09/16/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Role of GCNA in preserving genome integrity and fertility - PROJECT SUMMARY We propose a cross-species approach to understand the pathways that maintain genome integrity in germ cells. The perpetuation of the species requires that the genome is protected from endogenous and exogenous threats. Nowhere is this more critical than in the germ cells, the precursors of egg and sperm. Defects in the vigilance pathways lead to loss of genome integrity and subsequent deterioration of offspring vigor and/or miscarriage. Detailed studies of a newly identified, highly conserved genetic factor, GCNA (Germ Cell Nuclear Acidic Peptidase), will provide novel insights into key determinants of genome integrity and fertility. Our preliminary data show that loss of GCNA results genomic instability in both Drosophila and C. elegans, indicating conservation of function. The experiments outlined here will provide some of the first insights into the shared mechanisms by which conserved GCNA family members promote genomic integrity and fertility across species. We find that GCNA both interacts with Topoisomerase 2 and prevents the formation of DNA:protein crosslinks (DPCs). GCNA mutant animals display increased chromosome loss, mutation accumulation, and cell cycle defects, placing GCNA at the hub of multiple genome integrity processes. To explore the mechanisms underlying gcna functions in germ cell maintenance, we propose three specific aims: 1) to analyze the etiology of chromosome loss, and to determine the contribution of gcna to cell cycle regulation, 2) to characterize the interaction with topoisomerase 2, identify conserved binding partners, and illuminate the nature and etiology of DPCs, and 3) to understand the domain structure of GCNA and its functional relevance to human fertility.


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 = $0 )
2025	2022	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3240 CRAFT PL STE 100	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	4/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	1/6/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $452,706 )
2022	2022	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	9/1/2022	NON-COMPETING CONTINUATION	$452,706
														Subtotal = $452,706

Issue Date FY: 2021 ( Subtotal = $452,706 )
2021	2021	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	3	8/31/2021	NON-COMPETING CONTINUATION	$452,706
														Subtotal = $452,706

Issue Date FY: 2020 ( Subtotal = $577,513 )
2020	2020	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	2	9/15/2020	SUPPLEMENT FOR EXPANSION	$124,736
2020	2020	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	2	8/27/2020	NON-COMPETING CONTINUATION	$452,777
														Subtotal = $577,513

Issue Date FY: 2019 ( Subtotal = $487,105 )
2019	2019	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	9/16/2019	NEW	$487,105
														Subtotal = $487,105

Grand Total All Awards = $1,970,030

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Role of GCNA in preserving genome integrity and fertility

Award Number: R01GM127569

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: 09/16/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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