Mechanism of DNA damage tolerance

Figure 2 Regulation of DNA damage tolerance by proliferating cell nuclear antigen modification. PCNA is a homotrimer that can be modified at K164 by either ubiquitin or SUMO. It can also be sumoylated at K127. PCNA mono-ubiquitination (mono-Ub) by Rad6/Rad18 facilitates the recruitment of TLS polymerases thereby promoting TLS. Extension of mono-Ub with a K63-linked Ub chain (poly-Ub) by Rad5/Ubc13/Mms2 promotes Rad5-dependent error-free TS pathway. PCNA sumoylation recruits Srs2 that inhibits the salvage HR pathway. HR: Homologous recombination; K: Lysine; PCNA: Proliferating cell nuclear antigen; S: Synthesis; SUMO: Small ubiquitin-like modifier; TLS: Translesion synthesis; TS: Template switching; Ub: Ubiquitin.