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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 2016 2021

Adenosine Diphosphate
Recombinational DNA Repair
Double-Stranded DNA Breaks
DNA Damage

Research Output 2002 2019

  • 4061 Citations
  • 14 h-Index
  • 20 Article
  • 4 Review article
  • 3 Comment/debate
  • 3 Short survey

Mechanisms of DNA damage tolerance: post-translational regulation of PCNA

Leung, W., Baxley, R. M., Moldovan, G-L. & Bielinsky, A. K., Jan 1 2019, In : Genes. 10, 1, 10.

Research output: Contribution to journalReview article

Proliferating Cell Nuclear Antigen
DNA Damage
Post Translational Protein Processing
Genetic Recombination
2 Citations (Scopus)

DNA polymerase eta prevents tumor cell-cycle arrest and cell death during recovery from replication stress

Barnes, R. P., Tsao, W. C., Moldovan, G-L. & Eckert, K., Dec 1 2018, In : Cancer Research. 78, 23, p. 6549-6560 12 p.

Research output: Contribution to journalArticle

Cell Cycle Checkpoints
Cell Death
Genomic Instability
Cell Survival
1 Citations (Scopus)

Loss of E2F7 confers resistance to poly-ADP-ribose polymerase (PARP) inhibitors in BRCA2-deficient cells

Clements, K. E., Thakar, T., Nicolae, C., Liang, X., Wang, H-G. & Moldovan, G-L., Jan 1 2018, In : Nucleic Acids Research. 46, 17, p. 8898-8907 10 p.

Research output: Contribution to journalArticle

Recombinational DNA Repair
Tumor Biomarkers
DNA Replication
1 Citations (Scopus)

NFκB regulates p21 expression and controls DNA damage-induced leukemic differentiation

Nicolae, C., O'connor, M. J., Constantin, D. & Moldovan, G-L., Jul 5 2018, In : Oncogene. 37, 27, p. 3647-3656 10 p.

Research output: Contribution to journalArticle

DNA Damage
Myeloid Leukemia
Myeloid Cells
Clustered Regularly Interspaced Short Palindromic Repeats
Binding Sites
1 Citations (Scopus)

PARP10 promotes cellular proliferation and tumorigenesis by alleviating replication stress

Schleicher, E. M., Galvan, A. M., Imamura, Y., Moldovan, G-L. & Nicolae, C., Jan 1 2018, In : Nucleic Acids Research. 46, 17, p. 8908-8916 9 p.

Research output: Contribution to journalArticle

Cell Proliferation
HeLa Cells
Clustered Regularly Interspaced Short Palindromic Repeats