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. 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, alpha and beta, are produced by a conserved tissue-specific alternative splicing mechanism involving exons encoding the C termini of the polypeptides. DNA ligase III-alpha cDNA, which encodes a 103-kDa polypeptide, is expressed in all tissues and cells, whereas DNA ligase III-beta cDNA, which encodes a 96-kDa polypeptide, is expressed only in the testis. During male germ cell differentiation, elevated expression of DNA ligase III-beta 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-beta, the C-terminal 77 amino acids of DNA ligase III-alpha are replaced by a different 17- to 18-amino acid sequence. As reported previously, the 103-kDa DNA ligase III-alpha interacts with the DNA strand break repair protein encoded by the 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 involving the DNA ligase III-alpha x XRCC1 complex. The distinct biochemical properties of DNA ligase III-beta, in combination with the tissue- and cell-type-specific expression of DNA ligase III-beta mRNA, suggest that this form of DNA ligase III is specifically involved in the completion of homologous recombination events that occur during meiotic prophase.
Mackey
Z B
ZB
Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, 78245, USA.
Ramos
W
W
Levin
D S
DS
Walter
C A
CA
McCarrey
J R
JR
Tomkinson
A E
AE
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D003001:Cloning, Molecular; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger / Q000032:analysis; D011995:Recombination, Genetic; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D013090:Spermatocytes / Q000166:cytology / Q000201:enzymology*; D013737:Testis / Q000254:growth & development; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D029867:Xenopus Proteins; C000619352:Xrcc1 protein, mouse; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human; C000618818:Lig3 protein, mouse