Yolk protein factor 1 is a Drosophila homolog of Ku, the DNA-binding subunit of a DNA-dependent protein kinase from humans

Abstract

Yolk protein factor 1 (YPF1) is a heterodimeric DNA-binding protein from Drosophila melanogaster. In this report, we describe evidence that YPF1 is a homolog of Ku, a human autoimmune antigen that is the DNA-binding subunit of a DNA-dependent protein kinase. In vitro this kinase phosphorylates several transcription factors and, at the time of transcription initiation, the carboxyl-terminal domain of RNA polymerase II. We find that a cDNA clone for the smaller subunit (beta) of YPF1 encodes a 72-kDa protein that has extensive homology to the smaller subunit of the heterodimeric Ku protein (24% identity, 51% similarity over the entire 631 amino acid length). Further, the larger YPF1 subunit (alpha) shares immunological epitopes with the larger subunit of Ku. YPF1 and Ku also appear to bind DNA similarly. Southwestern blot experiments demonstrate that, like the Ku protein, the smaller YPF1 subunit binds DNA in the absence of the larger subunit. Further, cross-linking experiments indicate that, once again like the Ku protein, both subunits make contact with DNA when YPF1 binds as a heterodimer. YPF1 beta transcripts occur at low levels in all stages of Drosophila development except during oogenesis and early embryogenesis when they increase 25-fold. In situ hybridization localizes the beta gene to position 34C on the left arm of chromosome 2.