TI - ATM and Control of the Normal Number and Distribution of Crossovers Forming an Obligate Crossover . AB - In most organisms , nonexchange chromosomes occur rarely , giving rise to the concept of the obligate crossover [57] ( see Introduction ) . The mammalian XY pair shares homology only within the very small PAR , and as a result , the crossover frequency in males is elevated >100-fold in the PAR over the genome average . DSB frequency in the PAR must be elevated atleast 10-fold over the genome average to ensure that the PAR receives atleast one DSB. ( Up to 300 DSBs are estimated per 3x109 bp per haploid genome , or 1 DSB per 107 bp , while the mouse PAR is estimated to be [4] ) But it is also likely that a DSBs within this limited physical distance has a greater probability of being converted to a crossover than the "average" DSB on an autosome . Thus , we infer that one or more aspects of crossover control play a particularly important role within the PAR to ensure formation of the obligate crossover . By this reasoning , XY recombination should be uniquely sensitive to perturbations in crossover control as well as to other defects in interhomolog recombination more generally . Here , we demonstrate that Spo11+/-Atm-/- spermatocytes frequently contain an achiasmate X and Y pair . Spo11+/- spermatocytes have no such difficulty , hence this defect can be attributed specifically to the lack of ATM . While it is formally possible that the achiasmate XY configuration reflects a defect in sister chromatid cohesion , we favor the interpretation that ATM-deficient cells have difficulty in forming the obligate XY crossover because a crossover defect could account for frequent failure of XY homologous synapsis , as SC formation is thought to initiate at crossover-designated recombination sites ( reviewed in [36] , [49] ) . Several factors contribute to forming an obligate crossover . At least one DSB must form per chromosome pair and the proper recombination partner ( the homolog rather than the sister ) must be located and engaged . Furthermore , differentiation of individual recombination events into crossovers must also be controlled . This control involves a "decision" early in the recombination reaction that determines whether a given DSB will become a crossover rather than a noncrossover , plus enforcement of this decision to ensure formation of the correct recombinant product [8] , [11] . In principle , ATM could contribute to one or more of these processes . However , we consider it unlikely that a DSB deficit explains the frequent crossover failure in Spo11+/-Atm-/- spermatocytes : Spo11 heterozygosity itself does not cause an XY crossover problem , and absence of ATM does not significantly decrease numbers of RAD51 foci in a Spo11+/- background , suggesting that ATM deficiency does not reduce DSB frequency . Therefore , it is possible that the XY defect reflects a requirement for ATM in promoting the XY crossover per se . There are several nonexclusive possibilities . ATM may be required for proper designation of a crossover outcome , either as part of the regulation of the crossover versus .noncrossover decision or as part of the response to that decision once it has been made . This model would implicate ATM in crossover control , consistent with effects on autosomes ( see below ) and consistent with the observation that orthologs of ATM/ATR promote crossover interference in budding yeast via PHOSphorylation of the single-stranded binding protein RPA [58] . Another possibility is that crossover designation occurs properly in the absence of ATM , but that there is a defect in later steps of recombination such that crossover or chiasma formation fails . Notably , however , there was no detectable increase in achiasmate autosomes , suggesting that ATM is not strictly required for maturing chiasmata . A third possibility is that ATM is required for efficient homologous pairing and choice of partner for recombination ( ie , homolog versus sister ) . This hypothesis would place ATM function at or prior to the step when the homologous chromosome is located and engaged , i.e. , before a decision is made about a crossover versus .noncrossover outcome . Further studies of the kinetics and efficiency of homologous pairing in normal and ATM-deficient mouse meiosis are necessary to distinguish between these possibilities . However , it is interesting to note that budding yeast ATM/ATR orthologs are required to suppress recombination between ectopic repeated sequences and to promote the normal bias toward interhomolog rather than intersister recombination [27] , [28] . Why is there an obligate crossover defect on the XY but not on autosomes? One reasonable explanation is that the small size of the PAR makes this region uniquely sensitive to defects in any or all of the processes listed above . At ~55-58 Mbp , even the smallest autosome ( Chr19 ) is some 80 times as long as the PAR and forms on average 4-5 RPA and MSH4 foci , of which typically only one will give rise to a crossover [51] . The formation of multiple DSBs along each autosomal bivalent means that there are multiple opportunities to promote pairing and to successfully execute chiasma formation , such that a partial defect in pairing , in formation of crossovers , or in regulation of crossover number and distribution might have little effect on the frequency of non-exchange bivalents . In contrast , the XY pair may have as little as a single DSB within the PAR in any one cell , which would place a much greater premium on efficient execution of all of the steps that lead to chiasma formation .