TY - JOUR
T1 - Repriming of DNA synthesis at stalled replication forks by human PrimPol
AU - Mourón, Silvana
AU - Rodriguez-Acebes, Sara
AU - Martínez-Jiménez, María I.
AU - García-Gómez, Sara
AU - Chocrón, Sandra
AU - Blanco, Luis
AU - Méndez, Juan
N1 - Funding Information:
We thank all members of our laboratories for helpful discussions, S. Iwai (Osaka University) for the (6-4)pp oligonucleotide, Z.F. Pursell (Tulane University School of Medicine) for purified Polε, J.-S. Hoffmann (Cancer Research Center of Toulouse, France) for anti-Polη, M. Soengas (Spanish National Cancer Research Centre) for HDF cells, P. Delgado for assistance with lymphocyte isolation, M. Pérez and D. Megías for assistance with confocal microscopy and life cell imaging, M.F. Rodríguez-Tornos for her contribution to the early stages of this project, B. Urcelay for technical support in J.M.’s lab, and M. Serrano and A.R. Ramiro for helpful comments on the manuscript. This work was supported by Comunidad de Madrid (S2011/BMD-2361 to L.B.) and the Spanish Ministry of Economy and Competitiveness (BFU2010-21467 to J.M., BFU2012-37969 to L.B., Consolider CSD2007-00015 to L.B. and J.M.).
PY - 2013/12
Y1 - 2013/12
N2 - DNA replication forks that collapse during the process of genomic duplication lead to double-strand breaks and constitute a threat to genomic stability. The risk of fork collapse is higher in the presence of replication inhibitors or after UV irradiation, which introduces specific modifications in the structure of DNA. In these cases, fork progression may be facilitated by error-prone translesion synthesis (TLS) DNA polymerases. Alternatively, the replisome may skip the damaged DNA, leaving an unreplicated gap to be repaired after replication. This mechanism strictly requires a priming event downstream of the lesion. Here we show that PrimPol, a new human primase and TLS polymerase, uses its primase activity to mediate uninterrupted fork progression after UV irradiation and to reinitiate DNA synthesis after dNTP depletion. As an enzyme involved in tolerance to DNA damage, PrimPol might become a target for cancer therapy.
AB - DNA replication forks that collapse during the process of genomic duplication lead to double-strand breaks and constitute a threat to genomic stability. The risk of fork collapse is higher in the presence of replication inhibitors or after UV irradiation, which introduces specific modifications in the structure of DNA. In these cases, fork progression may be facilitated by error-prone translesion synthesis (TLS) DNA polymerases. Alternatively, the replisome may skip the damaged DNA, leaving an unreplicated gap to be repaired after replication. This mechanism strictly requires a priming event downstream of the lesion. Here we show that PrimPol, a new human primase and TLS polymerase, uses its primase activity to mediate uninterrupted fork progression after UV irradiation and to reinitiate DNA synthesis after dNTP depletion. As an enzyme involved in tolerance to DNA damage, PrimPol might become a target for cancer therapy.
UR - https://www.scopus.com/pages/publications/84890105942
UR - https://www.scopus.com/pages/publications/84890105942#tab=citedBy
U2 - 10.1038/nsmb.2719
DO - 10.1038/nsmb.2719
M3 - Article
C2 - 24240614
AN - SCOPUS:84890105942
SN - 1545-9993
VL - 20
SP - 1383
EP - 1389
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 12
ER -