Wednesday, October 15, 2025 10/15/2025

Mitochondrial translesion DNA synthesis

Award Number: R01GM145925
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: 04/28/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Mitochondrial translesion DNA synthesis - ABSTRACT Mitochondrial DNA (mtDNA) integrity is critical for metabolism and cellular energy supply and human health and longevity. Due to lack of repair mechanism and specified translesion synthesis (TLS) polymerase, mtDNA contains higher contents of UV lesions. The high-fidelity mitochondrial DNA polymerase (Pol g) will unavoidably encounter the UV lesions during mtDNA replication. Unlike other high-fidelity DNA polymerases that lack TLS activity, we found Pol g possesses a metal regulated TLS activity. In the presence of magnesium ion, Pol g exhibits no TLS activity, however, in the presence of physiological concentrations of manganese ion alone or Mg/Mn mixture, Pol g can synthesize cross UV lesion cyclobutane dimer with efficiency near that on the non-damaged DNA. We also discovered that Pol g has an extensive lesion recognition network that can sense an upstream lesion as far as 10 base pairs in the presence of Mg2+, but completely ignores the lesion with Mn2+. We hypothesize that Manganese ion can alter the elasticity of Pol g to be able to accommodate bulky lesions for translesion synthesis. we will test the hypothesis by completing the Specific Aims 1) Mechanism of Pol g integrated lesion bypassing, extension, and replication activities, 2) Investigation of Pol g long-range lesion sensing and 3) Biophysical basis for metal-directed Pol g TLS. The proposed studies will illustrate how mitochondrial replicase utilizing the essential metal ions to maintain genome integrity under UV radiation.


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 = $333,746 )
2025	2025	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Biomedical Research and Research Training	000	3	7/17/2025	NON-COMPETING CONTINUATION	$333,746
														Subtotal = $333,746

Issue Date FY: 2024 ( Subtotal = $333,746 )
2024	2024	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Biomedical Research and Research Training	000	2	3/20/2024	NON-COMPETING CONTINUATION	$300,371
2024	2024	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Biomedical Research and Research Training	001	2	6/24/2024	NON-COMPETING CONTINUATION	$33,375
														Subtotal = $333,746

Issue Date FY: 2023 ( Subtotal = $388,746 )
2023	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Biomedical Research and Research Training	000	1	4/28/2023	NEW	$388,746
														Subtotal = $388,746

Grand Total All Awards = $1,056,238

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Mitochondrial translesion DNA synthesis

Award Number: R01GM145925

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: 04/28/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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