English: Recombinational repair of DNA double-strand damage - some key steps. ATM (ATM) is a
protein kinase that is recruited and activated by
DNA double-strand breaks. DNA double-strand damages also activate the
Fanconi anemia core complex (FANCA/B/C/E/F/G/L/M).
[1] The FA core complex
monoubiquitinates the downstream targets FANCD2 and FANCI.
[2] ATM activates (phosphorylates)
CHEK2 and
FANCD2.
[3] CHEK2 phosphorylates BRCA1.
[4] Ubiquinated FANCD2 complexes with
BRCA1 and
RAD51.
[5] The PALB2 protein acts as a hub,
[6] bringing together BRCA1, BRCA2 and RAD51 at the site of a DNA double-strand break, and also binds to RAD51C, a member of the RAD51 paralog complex
RAD51B-
RAD51C-
RAD51D-
XRCC2 (BCDX2). The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.
[7] RAD51 plays a major role in
homologous recombinational repair of DNA during double strand break repair. In this process, an ATP dependent DNA strand exchange takes place in which a single strand invades base-paired strands of homologous DNA molecules. RAD51 is involved in the search for homology and strand pairing stages of the process.