Projects per year
Personal profile
Research interests
Dr. George-Lucian Moldovan’s major research goal is to elucidate the molecular mechanism of replication of DNA lesions in human cells, using an integrative approach that includes:
- identification of the factors involved in detection and processing of stalled forks;
- biochemical reconstitution of discrete steps of the fork restart process; and
- genetic analyses to assess the role of these processes in genomic stability, cellular transformation, and cancer prevention and therapy.
For all organisms, the information necessary for living and propagation is encoded in their genomes. Maintaining and transferring stable genomes to the progeny is thus essential. In humans, failure to preserve the correct DNA sequence can result in cellular transformation and cancer, as well as degeneration and accelerated aging. To avoid genomic instability, cells employ numerous mechanisms that detect, signal and repair DNA lesions. These mechanisms also stabilize and protect complex macromolecular structures such as replication forks (which form during DNA duplication) and ensure the correct and timely replication and segregation of chromosomes. They are subjected to complex cellular regulation and are frequently inactivated in cancer.
In particular, DNA replication is a complex process that requires tight regulation to ensure genomic stability. Replication of damaged DNA poses a great risk, since DNA lesions cannot be processed by regular replicative polymerases and thus result in stalling of the replication machinery. Understanding how the replication machinery deals with roadblocks is fundamental, since prolonged replication stalling can result in strand breaks, translocations, and genomic instability. What ultimately dictates the fate of stalled forks is not understood and in fact remains one of the biggest unsolved mysteries in cell biology.
To resolve this conundrum, the missing components of this regulatory circuit must be identified and characterized.
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Projects
- 1 Finished
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The Role of Mono-ADP-Ribosylation by PARP14 in Radioresistance
Moldovan, G. & MOLDOVAN, G. L.
National Institute of Environmental Health Sciences
2/1/16 → 1/31/21
Project: Research project
Research output
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Dual genome-wide CRISPR knockout and CRISPR activation screens identify mechanisms that regulate the resistance to multiple ATR inhibitors
Schleicher, E. M., Dhoonmoon, A., Jackson, L. M., Clements, K. E., Stump, C. L., Nicolae, C. M. & Moldovan, G. L., Nov 2 2020, In: PLoS genetics. 16, 11, e1009176.Research output: Contribution to journal › Article › peer-review
Open Access -
FANCJ compensates for RAP80 deficiency and suppresses genomic instability induced by interstrand cross-links
Awate, S., Sommers, J. A., Datta, A., Nayak, S., Bellani, M. A., Yang, O., Dunn, C. A., Nicolae, C. M., Moldovan, G. L., Seidman, M. M., Cantor, S. B. & Brosh, R. M., Sep 18 2020, In: Nucleic acids research. 48, 16, p. 9161-9180 20 p.Research output: Contribution to journal › Article › peer-review
Open Access1 Scopus citations -
Genome-wide CRISPR synthetic lethality screen identifies a role for the ADP-ribosyltransferase PARP14 in DNA replication dynamics controlled by ATR
Dhoonmoon, A., Schleicher, E. M., Clements, K. E., Nicolae, C. M. & Moldovan, G. L., Jul 27 2020, In: Nucleic acids research. 48, 13, p. 7252-7264 13 p.Research output: Contribution to journal › Article › peer-review
Open Access -
Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens
Clements, K. E., Schleicher, E. M., Thakar, T., Hale, A., Dhoonmoon, A., Tolman, N. J., Sharma, A., Liang, X., Imamura Kawasawa, Y., Nicolae, C. M., Wang, H. G., De, S. & Moldovan, G-L., Dec 2020, In: Nature communications. 11, 1, 6118.Research output: Contribution to journal › Article › peer-review
Open Access -
The Dopamine D2 Receptor Contributes to the Spheroid Formation Behavior of U87 Glioblastoma Cells
Weissenrieder, J. S., Reed, J. L., Green, M. V., Moldovan, G. L., Koubek, E. J., Neighbors, J. D. & Hohl, R. J., Jan 1 2020, In: Pharmacology. 105, 1-2, p. 19-27 9 p.Research output: Contribution to journal › Article › peer-review
Open Access5 Scopus citations