Figure 1
From: An update on targeted gene repair in mammalian cells: methods and mechanisms
Components involved in mammalian repair pathways. A: In mismatch repair (MMR), hMutSα recognizes the DNA damage whereby hMutLα is recruited resulting in nicks on either side of the mismatch. Human exonuclease I (hExoI, 5'→3' activity) excises the mismatch and its flanking sequences after which DNA polymerase (3'→5' activity), along with PCNA and RFC, re-synthesizes a new DNA strand. B: In nucleotide excision repair (NER), the XPC complex recognizes the DNA damage causing the recruitment of the TFIIH complex, which unwinds the DNA to an open complex. XPA binds the damaged DNA strand after which endonucleases, XPG and XPF-ERCC1, excise the mismatch and DNA polymerase, with PCNA and RFC re-synthesizes the DNA strand. C: In homology-directed repair (HDR), the DSB is bound by the MRN complex recruiting CtIP and hExo, the latter of which excise nucleotides surrounding the break. Rad51 initiates homology search and when a homologous DNA donor is found, the DSB is repaired through Holliday junction formation and resolution. D: In non-homologous end-joining (NHEJ), the Ku complex recognizes the DSB leading to a simultaneous recruitment of DNA-PKCS, XRCC4:LigIV and XLF. The exchange of these factors drives the ligation of the non-homologous ends. Artemis nuclease, DNA polymerases μ and λ and other protein factors can be involved if the DNA ends are not directly compatible. See text for further details.