Association of RAD52 with the RPA complex at resected DNA DSBs

RAD52 heptamers bind 3' overhanging ssDNA at resected DNA double-strand breaks (DSBs) by simultaneously interacting with the DNA and the RPA complex. The conformation of the RAD52-ssDNA complex is thought to place the ssDNA on an exposed surface of the ring, in a configuration that may promote the DNA-DNA annealing of complementary DNA strands (Parsons et al. 2000). The interaction with RPA is necessary for RAD52-mediated homology driven repair (Park et al. 1996, Jackson et al. 2002). Phosphorylation of RAD52 at tyrosine residue Y104 by ABL1 in response to ATM signaling increases the affinity of RAD52 for DNA (Kitao et al. 2002, Cramer et al. 2008, Honda et al. 2011). Long range resection, which results in the activation of ATR/CHEK1 signaling, is needed for RAD52-mediated single strand annealing (SSA). RAD52 function may be promoted by a direct interaction with WRN helicase which participates in long-range resection of DNA DSBs (Baynton et al. 2003).

RAD52七聚体通过与DNA和RPA复合物的同时相互作用，在切除的DNA双链断裂（DSBs）处结合3'悬突ssDNA。据推测，RAD52-ssDNA复合物的构象将ssDNA置于环的暴露表面，形成一种可能促进互补DNA链DNA-DNA退火（Parsons等，2000年）的构型。与RPA的相互作用对于RAD52介导的同源驱动修复（Park等，1996年，Jackson等，2002年）是必要的。在ATM信号传导的响应下，由ABL1在酪氨酸残基Y104对RAD52的磷酸化增加了RAD52对DNA的亲和力（Kitao等，2002年，Cramer等，2008年，Honda等，2011年）。长距离切除，导致ATR/CHEK1信号传导的激活，对于RAD52介导的单链退火（SSA）是必需的。RAD52的功能可能通过直接与参与DNA DSBs长距离切除的WRN解旋酶相互作用而得到促进（Baynton等，2003年）。