| Description |
There are a number of different names in use for DNA damage foci, such as (ionizing) radiation-induced foci (IRIF or RIF) or DNA repair foci. In general they all refer to local accumulations or modifications of DNA damage response proteins that form at the sites of DNA double-strand breaks and can be visualized through microscopic imaging following immunocyto- or -histochemical detection or fluorescent protein tagging. The first and most prominent protein for which foci formation at the site of a double strand break was described is the histone variant H2AX which gets phosphorylated at its C-terminal Ser-139 residue by the DNA damage-activated kinases ATM, ATR, and DNA-PK to form γH2AX. γH2AX then acts as a docking station for other DNA damage signaling factors such as MDC1 and 53BP1 which accumulate to form foci in a histone-modification-dependent manner[1]. IRIF are dynamic structures containing thousands of copies of proteins involved in various aspects of DSB repair and signaling. These proteins include phosphorylated ATM, 53BP1, MDC1, RAD51, MRN complex (MRE11/RAD50/NBS1), RNF8/KIAA0646, RNF168, and BRCA1-A complex (BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1)[2]. |