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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
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The multi-replication protein A (RPA) system--a new perspective.

Kengo Sakaguchi1, Toyotaka Ishibashi, Yukinobu Uchiyama

  • 1Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan. kengo@rs.noda.tus.ac.jp

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The multi-RPA complex, crucial for DNA replication and repair, exists in diverse forms across eukaryotes. Recent findings reveal distinct RPA complexes, each with unique roles in DNA metabolism.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Replication protein A (RPA) is essential for eukaryotic DNA metabolism, including replication, repair, telomere maintenance, and homologous recombination.
  • Previously, only one type of RPA complex was thought to exist in eukaryotes, but recent research indicates the presence of multiple distinct RPA complexes.

Purpose of the Study:

  • To review recent data on the function and biological importance of the multi-RPA complex.
  • To explore the composition and biological functions of various RPA complexes across eukaryotic kingdoms.

Main Methods:

  • In vivo and in vitro approaches were used to study RPA function.
  • Literature review of recent findings on RPA complex composition and biological roles.

Main Results:

  • Distinct RPA complexes exist in different biological kingdoms, challenging the long-held belief of a single eukaryotic RPA type.
  • Higher plants have three distinct large and medium subunits with one smallest subunit, forming stable complexes.
  • Humans possess two paralogs and one analog of RPA, indicating a multi-RPA system is universal in eukaryotes.
  • Paralogs, orthologs, analogs, and heterologs of DNA synthesis factors, including RPA, are ubiquitous in eukaryotes, with convergent evolution playing a significant role.

Conclusions:

  • The multi-RPA system is a universal feature of eukaryotes, with distinct complexes likely serving different roles in DNA metabolism.
  • The diversity of RPA complexes and related factors highlights the prevalence of convergent evolution in DNA synthesis processes across eukaryotic kingdoms.