Repair of single-strand breaks during the cell cycle - saturation of repair capacity

Imaging of recruitment of XRCC1 and PCNA to a predetermined number of DNA single-strand breaks (SSB) demonstrates that (i) short-patch base excision repair is active throughout the whole cell cycle and repairs SSBs in over 60% of nonreplicating cells, while long-patch BER is active in approximately 30% of nonreplicating cells, becomes inactive in the early S phase and shows activity again in the mid and late S phase (in 8 and 16% of cells, respectively), (ii) cells retain the capacity to respond to damage if the total number of SSBs induced within seconds does not exceed approximately 110, more breaks evoke no XRCC1 recruitment; (iii) within less than a second, a cell commits a part of the currently available pool of XRCC1 molecules to accumulation at the damage site. We hypothesize that a limit on the number of single-strand breaks that elicit the BER response can arise from limited poly-ADP-ribosylation.