Fig. 4. HR and NHEJ, the two major NHEJ pathways. For NHEJ, DSB ends are recognized by Ku, which binds and activates DNA-PKcs. DNA nucleases and X-family polymerases Pol λ or μ remodel DSB ends. The DSBs are ligated by the ligation complex containing Lig IV, XLF, PAXX, and XRCC4. For HR, ends are resected by the MRN/BRCA1/CtIP complex and then various nucleases, resulting in long stretches of RPA-coated ssDNA. RPA is replaced by Rad51 in a BRCA2 dependent manner, and Rad51 facilitates strand invasion of a homologous DNA sequence, which is used as a template for DNA synthesis. After synthesis, the resulting HR intermediates are resolved and the ends are ligated.