Fig. 1.

DSBs in S and G2 phases of the cell cycle, collapsed replication forks, and daughter-strand gaps all require HR for their repair. The effect of mild hyperthermia does not affect the ability of first responders, such as recruiting the Mre11 complex at DSB or RP-A binding to single-strand DNA. However, the recruitment of BRCA2 and RAD51 is affected, suggesting that somewhere in the HR pathway, there is susceptibility to heat-induced protein degradation. Although Krawczyk et al. (1) suggest that the target is BRCA2, it could be at multiple points along the BRCA2 pathway of HR, including BRCA1 and PALB2. In the absence of the key RP-A-to-RAD51 mediator, BRCA2, there is failure to carry out HR as observed by reduced RAD51 foci and reduced sister chromatid exchanges.