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Two DNA endonucleases, ERCC5 (XPG) and the complex of ERCC1 and ERCC4 (XPF), are recruited to the open bubble structure to form the incision complex that will excise the damaged oligonucleotide from the affected DNA strand (Dunand-Sauthier et al. 2005, Zotter et al. 2006, Riedl et al. 2003, Tsodikov et al. 2007, Orelli et al. 2010). The RPA heterotrimer coats the undamaged DNA strand, thus protecting it from the endonucleolytic attack (De Laat et al. 1998).
RAD52 is the key mediator of SSA. Activated ATM phosphorylates and activates ABL1, and activated ABL1 subsequently phosphorylates pre-formed RAD52 heptameric rings, increasing their affinity for ssDNA (Honda et al. 2011). Phosphorylated RAD52 binds phosphorylated RPA heterotrimers on 3'-ssDNA overhangs at resected DNA DSBs. RAD52 also binds RAD51 and prevents formation of invasive RAD51 nucleofilaments involved in HRR (Chen et al. 1999, Van Dyck et al. 1999, Parsons et al. 2000, Jackson et al. 2002, Singleton et al. 2002).
RAD52 promotes annealing of two 3'-ssDNA overhangs when highly homologous directed repeats are present in both 3'-ssDNA overhangs. Nonhomologous regions lying 3' to the annealed repeats are displaced as 3'-flaps (Parsons et al. 2000, Van Dyck et al. 2001, Singleton et al. 2002, Stark et al. 2004, Mansour et al. 2008). The endonuclease complex composed of ERCC1 and ERCC4 (XPF) is subsequently recruited to SSA sites through direct interaction between RAD52 and ERCC4, leading to cleavage of 3' flaps (Motycka et al. 2004, Al-Minawi et al. 2008). The identity of a DNA ligase that closes the remaining single strand nicks (SSBs) to complete SSA-mediated repair is not known.
SSA results in deletion of one of the annealed repeats and the intervening DNA sequence between the two annealed repeats and is thus mutagenic.
Deubiquitinating activity of the UVSSA:USP7 complex is needed for ERCC6 stability at repair sites. Non-histone nucleosomal binding protein HMGN1 and histone acetyltransferase p300 (EP300) remodel the chromatin around the damaged site, thus facilitating repair.
Dual incision of the lesion-containing oligonucleotide from the affected DNA strand is performed by two DNA endonucleases, the ERCC1:ERCC4 (ERCC1:XPF) complex and ERCC5 (XPG), which also participate in GG-NER. DNA polymerases delta, epsilon or kappa fill in the single stranded gap after dual incision and the remaining single strand nick is sealed by DNA ligases LIG1 or LIG3 (the latter in complex with XRCC1), similar to GG-NER. After the repair of DNA damage is complete, RNA Pol II resumes RNA synthesis.
For past and recent reviews, see Mellon et al. 1987, Svejstrup 2002, Hanawalt and Spivak 2008, Vermeulen and Fousteri 2013 and Marteijn et al. 2014.