English: Recruitment of the BRCA1 A complex to a DSB in mammals. (A) After a double strand break (DSB) is recognized, ATM phosphorylates the histone variant H2AX in proximity to the DSB, which is subsequently called γ-H2AX. (B) Next, the mono-ubiquitination of the phosphorylated H2AX occurs. It is unclear which protein facilitates this, but it is possible that RNF8 is responsible for the initial ubiquitination together with the E2 ligase UBC13 and MMS2. Another hypothesis is that BMI1 mono-ubiquitinates γ-H2AX before RNF8 is recruited, and RNF8 elongates the K63-linked ubiquitin chain. (C) With the help of HERC2, RNF168 is recruited and further elongates the ubiquitin chain, again with UBC13 and MMS2. (D) The ubiquitin chain is then recognized by RAP80, a part of the BRCA1 A complex. This complex then orchestrates DNA repair by bringing RAD51 to the DSB. (Proteins with a known homolog in Arabidopsis are colored and the names are written in bold; ABRA1, Abraxas; ATM, ataxia telangiectasia mutated; BARD1, BRCA1 associated RING domain protein 1; BRCA1, breast cancer susceptibility gene 1; BRCA2, breast cancer susceptibility gene 2; BRCC36, BRCA1/BRCA2 containing complex subunit 36; BRCC45, BRCA1/BRCA2 containing complex subunit 45; MDC1, mediator of DNA-damage checkpoint protein 1; NBA1, new component of the BRCA1 A complex; PALB2, partner and localizer of BRCA2; RAD51, radiation sensitive 51)