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@article{1825003, author = {Bailey, Laura J. and Teague, Rebecca and Kolesár, Peter and Bainbridge, Lewis J. and Lindsay, Howard D. and Doherty, Aidan J.}, article_location = {New York}, article_number = {49}, doi = {http://dx.doi.org/10.1126/sciadv.abh1004}, keywords = {POLO-LIKE KINASE-1; MITOCHONDRIAL-DNA REPLICATION; FORK REVERSAL; POLYMERASE ETA; PHOSPHORYLATION; CATASTROPHE; BYPASS; REPAIR; DOMAIN; ROLES}, language = {eng}, issn = {2375-2548}, journal = {Science Advances}, title = {PLK1 regulates the PrimPol damage tolerance pathway during the cell cycle}, url = {https://www.science.org/doi/10.1126/sciadv.abh1004}, volume = {7}, year = {2021} }
TY - JOUR ID - 1825003 AU - Bailey, Laura J. - Teague, Rebecca - Kolesár, Peter - Bainbridge, Lewis J. - Lindsay, Howard D. - Doherty, Aidan J. PY - 2021 TI - PLK1 regulates the PrimPol damage tolerance pathway during the cell cycle JF - Science Advances VL - 7 IS - 49 SP - 1-15 EP - 1-15 PB - American Association for the Advancement of Science SN - 23752548 KW - POLO-LIKE KINASE-1 KW - MITOCHONDRIAL-DNA REPLICATION KW - FORK REVERSAL KW - POLYMERASE ETA KW - PHOSPHORYLATION KW - CATASTROPHE KW - BYPASS KW - REPAIR KW - DOMAIN KW - ROLES UR - https://www.science.org/doi/10.1126/sciadv.abh1004 N2 - Replication stress and DNA damage stall replication forks and impede genome synthesis. During S phase, damage tolerance pathways allow lesion bypass to ensure efficient genome duplication. One such pathway is repriming, mediated by Primase-Polymerase (PrimPol) in human cells. However, the mechanisms by which PrimPol is regulated are poorly understood. Here, we demonstrate that PrimPol is phosphorylated by Polo-like kinase 1 (PLK1) at a conserved residue between PrimPol's RPA binding motifs. This phosphorylation is differentially modified throughout the cell cycle, which prevents aberrant recruitment of PrimPol to chromatin. Phosphorylation can also be delayed and reversed in response to replication stress. The absence of PLK1-dependent regulation of PrimPol induces phenotypes including chromosome breaks, micronuclei, and decreased survival after treatment with camptothecin, olaparib, and UV-C. Together, these findings establish that deregulated repriming leads to genomic instability, highlighting the importance of regulating this damage tolerance pathway following fork stalling and throughout the cell cycle. ER -
BAILEY, Laura J., Rebecca TEAGUE, Peter KOLESÁR, Lewis J. BAINBRIDGE, Howard D. LINDSAY and Aidan J. DOHERTY. PLK1 regulates the PrimPol damage tolerance pathway during the cell cycle. \textit{Science Advances}. New York: American Association for the Advancement of Science, 2021, vol.~7, No~49, p.~1-15. ISSN~2375-2548. Available from: https://dx.doi.org/10.1126/sciadv.abh1004.
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