RAD51-independent inverted-repeat recombination by a strand-annealing mechanism

Abstract

Recombination between inverted repeats is RAD52 dependent, but reduced only modestly in the rad51Δ mutant. RAD59 is required for RAD51-independent inverted-repeat recombination, but no clear mechanism for how recombination occurs in the absence of RAD51 has emerged. Because Rad59 is thought to function as an accessory factor for the single-strand annealing activity of Rad52 one possible mechanism for spontaneous recombination could be by strand annealing between repeats at a stalled replication fork. Here we demonstrate the importance of the Rad52 single-strand annealing activity for generating recombinants by showing suppression of the rad52Δ, rad51Δ rad52Δ and rad52Δ rad59Δ inverted-repeat recombination defects by the rfa1-D228Y mutation. In addition, formation of recombinants in the rad51Δ mutant was sensitive to the distance between the inverted repeats, consistent with a replication-based mechanism. Deletion of RAD5 or RAD18, which are required for error-free post-replication repair, reduced the recombination rate in the rad59Δ mutant, but not in wild type. These data are consistent with RAD51-independent recombinants arising by a faulty template switch mechanism that is distinct from nascent strand template switching.

SUMOylation of Rad52-Rad59 synergistically change the outcome of mitotic recombination

“…2B and C and [44]). Controlling Rad52 and Rad59 activity through SUMOylation could be particularly important to suppress non-conservative modes of recombinational repair at repetitive sequences, which may otherwise lead to translocations and telomere–telomere recombination [2,87–90]. …”

“…This Rad52-mediated repair pathway can be divided into two sub-pathways, depending on whether repair is RAD51 -dependent or -independent [1]. Notably, non-conservative RAD51 -independent HR via single-strand annealing (SSA) relies on the RAD52 paralogue RAD59 [2,3], and on RAD52 itself [4–8]. Similarly, break-induced replication, alternative lengthening of telomeres and inverted-repeat recombination can also proceed by either the Rad51 or Rad59 pathways [9–11], but the control of pathway choice is not fully understood.…”

A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

“…The observation that mre11⌬, rad50⌬, and xrs2⌬ mutations but not rad51⌬ and rad52⌬ muta- tions caused increased GCR rates when combined with an rnh203⌬ mutation could reflect the role of Mre11-Rad50-Xrs2 but not Rad51 or Rad52 in stabilizing and processing stalled replication forks (97,98). Similarly, Sgs1, Esc2, Esc4/Rtt107, the Mus81-Mms4 complex, and the sumoylation of PCNA, which is blocked by the pol30-119 mutation, play roles in the processing of stalled replication forks (69,76,80,87).…”

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

“…In this regard, Mgm101 shares similar molecular organization with Rad59. Rad59 has been reported to promote Rad51-independent inverted repeat recombination by a strand annealing mechanism (56).…”