Tuesday, November 4, 2025 11/4/2025

Structure and Mechanism of Non-Homologous End Joining

Award Number: R01GM135651
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: 02/11/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Structure and Mechanism of Non-Homologous End Joining - Summary Among all different types of DNA damages, double strand breaks (DSBs) are viewed as the most toxic ones that lead to genome instability. They are created by either endogenous agents such as reactive oxygen species, or exogenous ionizing radiation and chemicals. Unrepaired DSBs drive apoptosis and senescence, and incorrect DSB repair can lead to undesired genome rearrangements, such as deletions, translocations, and fusions. Non-homologous end-joining (NHEJ) pathway, in which the two broken DNA ends are directly ligated without referring to a homologous template, is the primary DSB repair pathway that remains active throughout the cell cycle. NHEJ is also responsible for the assembly of gene segments in V(D)J recombination, where various immunoglobulin genes are generated by exon recombination in immune cells. NHEJ is initialized by Ku heterodimer (Ku70/80) recognizing DSB ends. Upon recognizing a dsDNA broken end, Ku70/80 recruits the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and assembles into the so-called DNA-PK holoenzyme. Other evolutionarily conserved NHEJ factors, including components of the ligase complex (DNA ligase IV, XRCC4 and XLF) are then recruited to the end reparation site. Successful DSB repair through NHEJ relies on the efficient bridging of two broken DNA ends, and this proposal aims to investigate the mechanism of NHEJ by directly visualizing the key steps of repair using single-particle cryo-EM. A more refined picture of the system specifically recognizing and correcting DSBs will provide an unprecedented, comprehensive view of these essential molecular machines during operation, and could lead to the development of novel treatments for various types of human cancer.


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 = $16,287 )
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	6	1/24/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$203,969
2025	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	5	1/24/2025	NON-COMPETING CONTINUATION	-$187,682
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	005	6	4/10/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
2025	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	004	5	4/10/2025	NON-COMPETING CONTINUATION	-$1
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	003	6	1/28/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1
2025	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	002	5	1/28/2025	NON-COMPETING CONTINUATION	$1
														Subtotal = $16,287

Issue Date FY: 2024 ( Subtotal = $345,573 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	5	1/18/2024	NON-COMPETING CONTINUATION	$311,016
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	5	6/25/2024	NON-COMPETING CONTINUATION	$34,557
														Subtotal = $345,573

Issue Date FY: 2023 ( Subtotal = $345,573 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	4	1/18/2023	NON-COMPETING CONTINUATION	$311,016
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	4	3/9/2023	NON-COMPETING CONTINUATION	$34,557
														Subtotal = $345,573

Issue Date FY: 2022 ( Subtotal = $345,573 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	3	7/28/2022	NON-COMPETING CONTINUATION	$34,557
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	3	1/5/2022	NON-COMPETING CONTINUATION	$311,016
														Subtotal = $345,573

Issue Date FY: 2021 ( Subtotal = $345,573 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	2	3/16/2021	NON-COMPETING CONTINUATION	$34,557
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	2	1/20/2021	NON-COMPETING CONTINUATION	$311,016
														Subtotal = $345,573

Issue Date FY: 2020 ( Subtotal = $360,229 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	1	2/11/2020	NEW	$360,229
														Subtotal = $360,229

Grand Total All Awards = $1,758,808

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Structure and Mechanism of Non-Homologous End Joining

Award Number: R01GM135651

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: 02/11/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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