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How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication.
<div class='caption-title'>Structure of Pol α-primase in the budding yeast replisome</div>
<div class='caption-title'>The structural basis for Pol α-primase recruitment to the budding yeast replisome</div>
Jones ML, Aria V, Baris Y, Yeeles JTP
OpenAccess logo Mol Cell (2023)
Related entries: 8b9a, 8b9b, 8b9d

Cited: 6 times
EuropePMC logo PMID: 37506699

Abstract

During eukaryotic DNA replication, Pol α-primase generates primers at replication origins to start leading-strand synthesis and every few hundred nucleotides during discontinuous lagging-strand replication. How Pol α-primase is targeted to replication forks to prime DNA synthesis is not fully understood. Here, by determining cryoelectron microscopy (cryo-EM) structures of budding yeast and human replisomes containing Pol α-primase, we reveal a conserved mechanism for the coordination of priming by the replisome. Pol α-primase binds directly to the leading edge of the CMG (CDC45-MCM-GINS) replicative helicase via a complex interaction network. The non-catalytic PRIM2/Pri2 subunit forms two interfaces with CMG that are critical for in vitro DNA replication and yeast cell growth. These interactions position the primase catalytic subunit PRIM1/Pri1 directly above the exit channel for lagging-strand template single-stranded DNA (ssDNA), revealing why priming occurs efficiently only on the lagging-strand template and elucidating a mechanism for Pol α-primase to overcome competition from RPA to initiate primer synthesis.

Articles - 8b9c mentioned but not cited (1)

  1. How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication. Jones ML, Aria V, Baris Y, Yeeles JTP. Mol Cell 83 2911-2924.e16 (2023)


Reviews citing this publication (2)

  1. Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism. Nasheuer HP, Meaney AM, Hulshoff T, Thiele I, Onwubiko NO. Int J Mol Sci 25 588 (2024)
  2. The Response of the Replication Apparatus to Leading Template Strand Blocks. Bellani MA, Shaik A, Majumdar I, Ling C, Seidman MM. Cells 12 2607 (2023)

Articles citing this publication (3)

  1. DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in Caenorhabditis elegans. Xia Y, Sonneville R, Jenkyn-Bedford M, Ji L, Alabert C, Hong Y, Yeeles JTP, Labib KPM. Science 381 eadi4932 (2023)
  2. Distinct RPA functions promote eukaryotic DNA replication initiation and elongation. Pike AM, Friend CM, Bell SP. Nucleic Acids Res 51 10506-10518 (2023)
  3. PRIMPOL ensures robust handoff between on-the-fly and post-replicative DNA lesion bypass. Mellor C, Nassar J, Šviković S, Sale JE. Nucleic Acids Res 52 243-258 (2024)


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