Image: Mattias Pettersson
Research group Our group studies dNTPs and maintenance of genome stability.
The four dNTPs (deoxyribonucleoside triphosphates dATP, dTTP, dCTP, and dGTP) are the essential building blocks of DNA. A balanced supply and appropriate overall concentration of dNTPs are critical for accurate genome replication. These requirements — together with the fact that dNTP levels fluctuate throughout the cell cycle — necessitate tight regulation of dNTP production through multiple mechanisms.
Our research focuses on:
(i) how the genome integrity checkpoint regulates dNTP concentrations, and conversely, how dNTP levels influence the activation of this checkpoint; and
(ii) how imbalanced dNTP pools affect replication fidelity and genome stability, including the recognition and repair of different types of replication errors.
Ultimately, we aim to uncover how metabolic changes in dNTP pool balance contribute to aging, cancer development, and other genetic disorders.
Awoyomi OF, Gorospe CM, Das B, Mishra P, Sharma S, Diachenko O, Nilsson AK, Tran P, Wanrooij PH and Chabes A (2025) RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis. PNAS 122:e2503531122. doi: 10.1073/pnas.2503531122
Tran P, Mishra P, Williams LG, Moskalenko R, Sharma S, Nilsson AK, Watt DL, Andersson P, Bergh A, Pursell ZF and Chabes A (2024) Altered dNTP pools accelerate tumor formation in mice. Nucleic Acids Res 52(20):12475-12486
Das B, Mishra P, Pandey P, Sharma S, Chabes A. (2022) dNTP concentrations do not increase in mammalian cells in response to DNA damage. Cell Metab. 34:1895-1896
Wanrooij PH, Tran P, Thompson LJ, Carvalho G, Sharma S, Kreisel K, Navarrete C, Feldberg AL, Watt DL, Nilsson AK, Engqvist MKM, Clausen AR and Chabes A (2020) Elimination of rNMPs from mitochondrial DNA has no effect on its stability. PNAS 117:14306-14313
Sushma S, Koolmeister C, Tran P, Nilsson AK, Larsson NG and Chabes A (2020) Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos. Nature Metabolism doi.org/10.1038/s42255-020-0264-z
Full publication list in PubMed (by date) and in Google Scholar (by citations).
