DNA double-strand breaks (DSBs) occur spontaneously during DNA replication and after exposure to certain genotoxic chemicals or ionizing radiation. Efficient repair of DSBs can be accomplished by nonhomologous end joining (NHEJ), which directly rejoins broken DNA ends, or by homologous recombination (HR), which utilizes a homologous DNA template to restore the genetic information lost at the break site (reviewed in 
). Failure to repair DSBs can lead to genome instability and cell death.
HR is initiated by 5′-3′ nucleolytic degradation of the DSB ends to yield 3′-ended single-stranded DNA (ssDNA) tails. Replication protein A (RPA) binds to the ssDNA tails to remove their secondary DNA structures, but is then replaced by Rad51 aided by Rad52. Once formed, the Rad51 nucleofilaments search for homologous sequences and then promote invasion of the ssDNA into homologous donor double-stranded DNA to form a joint molecule with a displaced strand (D-loop) (reviewed in 
). Following strand invasion, the 3′ end of the invading strand primes DNA synthesis using the donor sequence as a template, thus restoring those residues that were lost by resection 
According to the canonical double-strand break repair (DSBR) model 
, the displaced strand of the D-loop can anneal with the complementary sequence on the other side of the break (second end capture) to form a double Holliday junction (dHJ) intermediate. Random cleavage of the two HJs is expected to yield an equal number of noncrossover and crossover products. This DSBR model predicts that both crossover and noncrossover products derive from dHJ resolution. However, the finding that most DSB repair in somatic cells is not associated with crossovers 
led to alternative models for noncrossover generation. In one of them, the action of helicases mediates the convergent branch migration of the two HJs, thus producing a hemicatenane structure that is decatenated to form exclusively noncrossover products 
. A second mechanism, termed synthesis-dependent strand annealing (SDSA), leads to displacement of the invading strand that has been extended by DNA synthesis and that anneals with the complementary sequences exposed by 5′-3′ resection 
. Because no HJ is formed, only noncrossover products are made. Interestingly, during meiotic recombination, where dHJ resolution into crossovers is essential to drive segregation of homologs to opposite poles, most crossovers are thought to arise via dHJ resolution, whereas noncrossovers form mostly by the SDSA pathway 
When a DSB is flanked by direct repeats, its repair primarily occurs by single-strand annealing (SSA). Here, the resected DSB ends anneal with each other instead of invading a homologous DNA sequence (reviewed in 
). Subsequent nucleolytic removal of the protruding single-stranded tails results in deletion of the intervening DNA sequence and one of the repeats. In principle, such a break can also be repaired by break-induced replication (BIR), where the repeat closer to the cut site can strand-invade the repeat that is further away and set up a recombination-dependent replication fork to copy all the distal sequences. However, SSA usually out-competes BIR, which is a kinetically slow process 
All the above HR pathways require 5′-3′ nucleolytic degradation of DNA ends and the strand-annealing activity of Rad52. In addition, DSBR, SDSA and BIR require the Rad51 protein, which is dispensable for SSA that does not involve strand invasion 
In Saccharomyces cerevisiae
haploid cells, mitotic HR is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as an appropriate donor 
. This cell-cycle specificity depends on cyclin-dependent kinases (Cdks; Cdk1 in S. cerevisiae
), which promote resection of the 5′ DSB ends to yield 3′-ended ssDNA tails that are necessary to initiate HR 
. End resection occurs through a biphasic mechanism: first the MRX complex and Sae2 clip 50–100 nucleotides from the 5′ DNA ends; then Exo1 or Sgs1-Top3-Rmi1 and Dna2 process the early intermediate to form extensive regions of ssDNA (reviewed in 
). The Sae2 protein has been shown to be a Cdk1 target in promoting ssDNA generation at DNA ends during both mitosis and meiosis 
. However, as Sae2 only resects a relatively small amount of DNA and other nucleases and helicases are required for efficient DSB resection, Cdk1 likely has additional targets in promoting this event.
Indeed, DSB end resection is also negatively regulated by the Yku heterodimer 
and by the checkpoint protein Rad9 
. Interestingly, the ends of an endonuclease-induced DSB are resected in the G1 phase of the cell cycle (low Cdk1 activity) when Yku is lacking 
. Moreover, RAD9
deletion allows DSB resection in G2 cells that display low Cdk1 activity due the overexpression of the Cdk1 inhibitor Sic1 
. These findings indicate that Cdk1 requirement for DSB resection is bypassed when the inhibitory function of either Yku or Rad9 is relieved.
Whether Cdk1 promotes other HR events is unknown. Some evidence suggests that HR steps other than DSB resection might be regulated by Cdk1 activity. For example, formation of Rad52 foci after ionizing radiation (IR) is less efficient in G1 than in G2, suggesting that Cdk1 might control Rad52 recruitment to DSBs 
. Furthermore, Cdk1 targets the Srs2 helicase to dismantle D-loop structures, possibly by counteracting unscheduled Srs2 sumoylation 
. Proteins implicated in late HR events have also been identified as potential Cdk substrates in other eukaryotes. In particular, human BRCA2 is phosphorylated by Cdks, and this phosphorylation has been proposed to negatively regulate Rad51 recombination activity 
. Moreover, Cdk1-dependent phosphorylation of the fission yeast checkpoint protein Crb2 stimulates resolution of HR intermediates by the topoisomerase Top3 and the ReqQ helicase Rqh1 
Here, we investigate the role of Cdk1 in homology-dependent repair of a DSB. We show that generation of 3′-ended ssDNA at the DSB ends bypasses Cdk1 requirement for the repair of a DSB by either SSA or noncrossover recombination, indicating that Cdk1 is dispensable for these repair events if DSB resection occurs. By contrast, resection is not sufficient to bypass Cdk1 requirement for generating crossover products. Thus, Cdk1 promotes SSA- and noncrossover-mediated recombination by regulating essentially the resection step, while Cdk1 controls further HR steps in order to allow crossover outcomes.