【多选题】How does nonhomologous end joining (NHEJ) repair DNA double-strand breaks in eukaryotes?
A.
The reaction is initiated at the broken ends of a double-strand break by the binding of a heterodimer consisting of the proteins Ku70 and Ku80. The Ku proteins are conserved in almost all eukaryotes and act as a kind of molecular scaffold to assemble the other protein components.
B.
Ku70-Ku80 interacts with another protein complex containing a protein kinase called DNA-PKcs and a nuclease known as Artemis. Once the complex is assembled, the two broken DNA ends are synapsed (held together). DNA-PKcs autophosphorylates in several locations and also phosphorylates Artemis.
C.
Artemis, when phosphorylated, acquires an endonuclease function that can remove 5′ or 3′ single-stranded extensions or hairpins that might be present at the ends. The DNA ends are then separated with the aid of a helicase, and strands from the two different ends are annealed at locations where short regions of complementarity are encountered.
D.
Artemis cleaves any unpaired DNA segments that are created. Small DNA gaps are filled by a DNA polymerase, Pol μ or Pol λ. Finally, the nicks are sealed by a protein complex consisting of XRCC4 (X-ray cross complementation group), XLF (XRCC4-like factor), and DNA ligase IV.