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LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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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,...
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Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
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DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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Arrested replication forks guide retrotransposon integration.

Jake Z Jacobs1, Jesus D Rosado-Lugo1, Susanne Cranz-Mileva1

  • 1Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Nelson A133, 604 Allison Road, Piscataway, NJ 08854, USA.

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Summary

Fission yeast retrotransposon Tf1 insertion is guided by the DNA-binding protein Sap1. Sap1 acts as a replication fork barrier, directing Tf1 integration to specific genomic sites.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Epigenetics

Background:

  • Long terminal repeat (LTR) retrotransposons are mobile genetic elements that replicate via insertion into host genomes.
  • Fungal LTR retrotransposons possess mechanisms to avoid mutagenic insertions, particularly in coding sequences, but target selection principles remain unclear.

Purpose of the Study:

  • To investigate the conserved principles guiding target site selection for fungal LTR retrotransposon insertion.
  • To elucidate the role of the DNA-binding protein Sap1 in the targeting of the fission yeast LTR retrotransposon Tf1.

Main Methods:

  • Utilized genetic and molecular biology techniques in fission yeast.
  • Investigated the interaction between the Tf1 retrotransposon and the DNA-binding protein Sap1.
  • Assessed the function of Sap1 as a replication fork barrier in relation to Tf1 insertion.

Main Results:

  • Demonstrated that Sap1 directly guides the insertion of the Tf1 retrotransposon.
  • Showed that Sap1's activity as a replication fork barrier influences Tf1 targeting efficiency and location.
  • Identified a novel mechanism of retrotransposon integration targeting.

Conclusions:

  • Sap1 and the replication fork arrest it induces are key determinants of Tf1 integration sites.
  • This mechanism involves tethering the Tf1 integration complex to specific target sites, ensuring non-mutagenic insertion.
  • Provides insights into the conserved principles of LTR retrotransposon target site selection.