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

Three mammalian genes encoding DNA ligases have been identified. Howev er, the role of each of these enzymes in mammalian DNA metabolism has not been established. In this study, we show that two forms of mammali an DNA ligase III, alpha and beta, are produced by a conserved tissue- specific alternative splicing mech anism involving exons encoding the C termini of the polypeptides. DNA ligase III-alpha cDNA, which encode s a 103-kDa polypeptide, is expressed in all tissues and cells, wherea s DNA ligase III-beta cDNA, which encodes a 96-kDa polypeptide, is exp ressed only in the testis, During male germ cell differentiation, elev ated expression of DNA ligase III-beta mRNA is restricted, beginning o nly in the latter stages of meiotic prophase and ending in the round s permatid stage. In 96-kDa DNA ligase III-beta, the C-terminal 77 amino acids of DNA ligase III-alpha are replaced by a different 17- to 18-a mino acid sequence. As reported previously, the 103-kDa DNA ligase III -alpha interacts with the DNA strand break repair protein encoded by t he human XRCC1 gene. In contrast, the 96-kDa DNA ligase III-beta does not interact with XRCC1, indicating that DNA ligase III-beta may play a role in cellular functions distinct from the DNA repair pathways inv olving the DNA ligase III-alpha XRCC1 complex. The distinct biochemica l properties of DNA ligase III-beta, in combination with the tissue- a nd cell-type-specific expression of DNA ligase III-beta mRNA, suggest that this form of DNA ligase III is specifically involved in the compl etion of homologous recombination events that occur during meiotic pro phase.