TI - Colocalization of Axis Defects with Sites of Double Strand Break Repair . AB - One role of ATM in early meiotic prophase is to promote the PHOSphorylation of H2AX in response to SPO11-generated DSBs [20] , [32] . In Atm-/- spermatocytes , gammaH2AX is nearly absent in leptonema and much reduced in zygonema [20] , [32] , and similar patterns have been shown in Spo11+/-Atm-/- spermatocytes [32] ( see Figure S3A , S3B , S3C and S3D ) , indicating that rescue of meiotic progression is not associated with restoration of normal patterns of H2AX PHOSphorylation . It is important to note , however , that even in the absence of ATM , some gammaH2AX does form on autosomes in response to SPO11-generated DSBs , presumably due to the activity of the ATM-related kinase ATR [20] , [32] . As previously noted [32] , pachytene and diplotene Spo11+/-Atm-/- spermatocytes showed bright puffs of gammaH2AX staining at both interstitial and telomeric positions on chromosome axes that had normal SYCP3 patterns ( 80/570 chromosomes = 140% ; 43 cells ) ( Figures 5J and S3F ) . Such staining is aberrant because gammaH2AX largely disappears from the autosomes by mid-pachynema in normal spermatocytes [44] (Figure S3E) . These results , along with persistent foci of DSB repair proteins such as RAD51 [32] (Figure 5K) and the single strand binding protein RPA (Figure 5L) , suggest the presence of persistent DSBs ( or de novo DSB formation ) in Spo11+/-Atm-/- spermatocytes . Importantly , many SYCP3 abnormalities were associated with these cytological markers of DSB repair : gammaH2AX was present at 59% of SYCP3 gaps ( n = 66 gaps ) and at the non-telomeric ends of 72.3% of short SC fragments ( n = 101 fragments ) ( Figure 5J ) ; RAD51 foci were present at 38.2% of SYCP3 gaps ( n = 68 ) ( Figure 5K ) and at the non-telomeric ends of 50% of short SC fragments ( n = 62 ) ; and RPA foci were present at 50.9% of gaps ( n = 114 ) and at the non-telomeric ends of 57.1% of short SC fragments ( n = 91 ) (Figure 5L) . The frequent association of SYCP3 anomalies with DSB markers suggests a possible mechanistic link between chromosome axis defects and the ongoing process of DSB repair ( see Discussion ) .