Timothée Laurent
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Timothée Laurent has a total of 8 co-authors. Here are the top co-authors by number of shared publications:
- Aldo Emmanuel Pérez-Rivera
Centro de Biologica Molecular Severo Ochoa, E-28049 Madrid, Spain.
1 shared publication - Cristina Velázquez-Ruiz
Centro de Biología Molecular Severo Ochoa, (CSIC-UAM), c/Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain
1 shared publication - Gorazd Stojkovič
Department of Medical Biochemistry and Biophysics, Umeå University, 90 187 Umeå, Sweden
1 shared publication - Kazutoshi Kasho
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582
1 shared publication - Louise Jenninger
Department of Medical Biochemistry and Cell Biology, University of Gothenburg, 405 30 Gothenburg, Sweden
1 shared publication - Luis Blanco
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), C/ Nicolás Cabrera 1, Madrid 28049 (Spain)
1 shared publication
Latest Publications
- Open Access
A unique arginine cluster in PolDIP2 enhances nucleotide binding and DNA synthesis by PrimPol
Replication forks often stall at damaged DNA. Resumption of DNA synthesis can occur by replacement of the replicative DNA polymerase with specialized, error-prone translesion DNA polymerases (TLS), that have higher tolerance for damaged substrates. Several of these polymerases (Polλ, Polη and PrimPol) are stimulated in DNA synthesis through interaction with PolDIP2, however the mechanism of this PolDIP2-dependent stimulation is still unclear. Here we show that PrimPol uses a flexible loop to interact with the C-terminal ApaG-like domain of PolDIP2, and that this contact is essential for PrimPol’s enhanced processivity. PolDIP2 increases PrimPol’s primer-template and dNTP binding affinity, which concomitantly enhances PrimPol’s nucleotide incorporation efficiency. This activity is dependent on a unique arginine cluster in PolDIP2 and could be essential for PrimPol to function in vivo , since the polymerase activity of PrimPol alone is very limited. This mechanism, where the affinity for dNTPs gets increased by PolDIP2 binding, could be common to all other PolDIP2-interacting TLS polymerases, i.e. Polλ, Polη, Polζ and REV1, and might be critical for their in vivo function of tolerating DNA lesions at physiological nucleotide concentrations.
Open AccessA unique arginine cluster in PolDIP2 enhances nucleotide binding and DNA synthesis by PrimPol
Replication forks often stall at damaged DNA. Resumption of DNA synthesis can occur by replacement of the replicative DNA polymerase with specialized, error-prone translesion DNA polymerases (TLS), that have higher tolerance for damaged substrates. Several of these polymerases (Polλ, Polη and PrimPol) are stimulated in DNA synthesis through interaction with PolDIP2, however the mechanism of this PolDIP2-dependent stimulation is still unclear. Here we show that PrimPol uses a flexible loop to interact with the C-terminal ApaG-like domain of PolDIP2, and that this contact is essential for PrimPol’s enhanced processivity. PolDIP2 increases PrimPol’s primer-template and dNTP binding affinity, which concomitantly enhances PrimPol’s nucleotide incorporation efficiency. This activity is dependent on a unique arginine cluster in PolDIP2 and could be essential for PrimPol to function in vivo , since the polymerase activity of PrimPol alone is very limited. This mechanism, where the affinity for dNTPs gets increased by PolDIP2 binding, could be common to all other PolDIP2-interacting TLS polymerases, i.e. Polλ, Polη, Polζ and REV1, and might be critical for their in vivo function of tolerating DNA lesions at physiological nucleotide concentrations.