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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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