title: Archaeal replicative primases can perform translesion DNA synthesis.
abstract: DNA replicases routinely stall at lesions encountered on the template strand, and translesion DNA synthesis (TLS) is used to rescue progression of stalled replisomes. This process requires specialized polymerases that perform translesion DNA synthesis. Although prokaryotes and eukaryotes possess canonical TLS polymerases (Y-family Pols) capable of traversing blocking DNA lesions, most archaea lack these enzymes. Here, we report that archaeal replicative primases (Pri S, primase small subunit) can also perform TLS. Archaeal Pri S can bypass common oxidative DNA lesions, such as 8-Oxo-2'-deoxyguanosines and UV light-induced DNA damage, faithfully bypassing cyclobutane pyrimidine dimers. Although it is well documented that archaeal replicases specifically arrest at deoxyuracils (dUs) due to recognition and binding to the lesions, a replication restart mechanism has not been identified. Here, we report that Pri S efficiently replicates past dUs, even in the presence of stalled replicase complexes, thus providing a mechanism for maintaining replication bypass of these DNA lesions. Together, these findings establish that some replicative primases, previously considered to be solely involved in priming replication, are also TLS proficient and therefore may play important roles in damage tolerance at replication forks.
authors: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, United Kingdom.
authors: Stanislaw K
authors: SK
authors: Jozwiakowski
authors: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, United Kingdom.
authors: Farimah
authors: F
authors: Borazjani Gholami
authors: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, United Kingdom ajd21@sussex.ac.uk.
authors: Aidan J
authors: AJ
authors: Doherty
mesh_terms: D001105:Archaea / Q000201:enzymology*; D055162:Biocatalysis; D004249:DNA Damage; D019915:DNA Primase / Q000378:metabolism*; D019641:DNA, Archaeal / Q000096:biosynthesis*; D018384:Oxidative Stress
chemical_list: D019641:DNA, Archaeal; D019915:DNA Primase
keywords: AEP; archaea; primase; replication; translesion synthesis
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