An alternative splicing event which occurs in mouse pachytene spermatocytes generates a form of DNA ligase III with distinct biochemical properties that may function in meiotic recombination

Zachary B. Mackey, William Ramos, David S. Levin, Christi A. Walter, John R. Mccarrey, Alan E. Tomkinson

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Three mammalian genes encoding DNA ligases have been identified. However, the role of each of these enzymes in mammalian DNA metabolism has not been established. In this study, we show that two forms of mammalian DNA ligase III, α and β, are produced by a conserved tissue-specific alternative splicing mechanism involving exons encoding the C termini of the polypeptides. DNA ligase III-α cDNA, which encodes a 103-kDa polypeptide, is expressed in all tissues and cells, whereas DNA ligase III-β cDNA, which encodes a 96-kDa polypeptide, is expressed only in the testis. During male germ cell differentiation, elevated expression of DNA ligase III-β mRNA is restricted, beginning only in the latter stages of meiotic prophase and ending in the round spermatid stage. In 96-kDa DNA ligase III-β, the C- terminal 77 amino acids of DNA ligase III-α are replaced by a different 17- to 18-amino acid sequence. As reported previously, the 103-kDa DNA ligase III-α interacts with the DNA strand break repair protein encoded by the human XRCC1 gene. In contrast, the 96-kDa DNA ligase III-β does not interact with XRCC1, indicating that DNA ligase III-β may play a role in cellular functions distinct from the DNA repair pathways involving the DNA ligase III- α·XRCC1 complex. The distinct biochemical properties of DNA ligase III-β, in combination with the tissue- and cell-type-specific expression of DNA ligase III-β mRNA, suggest that this form of DNA ligase III is specifically involved in the completion of homologous recombination events that occur during meiotic prophase.

Original languageEnglish (US)
Pages (from-to)989-998
Number of pages10
JournalMolecular and cellular biology
Volume17
Issue number2
DOIs
StatePublished - Feb 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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