Abstract
The DNA damage response (DDR) requires a complex network of proteins that detect DNA damage, promote repair, and coordinate DNA repair with the cell cycle. The SQEF/Y C-terminal motif of histone H2A.X is rapidly phosphorylated (γH2A.X) upon induction of DNA damage. However, readers of this modification in plants have remained elusive. In animals mediator of DNA damage checkpoint 1 (MDC1) binds γH2A.X through a BRCA1 carboxyl-terminal (BRCT) domain. Individual BRCT domains or tandem BRCT domains (tBRCT) bind phosphorylated peptides and are predominantly associated with proteins involved in the DDR. Here, we performed a systematic analysis of BRCT domain proteome in Arabidopsis. Among 21 BRCT domain proteins, we identified BCP4 as a candidate ortholog of human MDC1. The C-terminal tBRCT domain of BCP4 bound γH2A.X in vitro and BCP4 localized into DNA damage-induced foci that were H2A.X dependent. We also show that although BCP1 has a dual tBRCT domain protein, it does not bind to γH2A.X, but co-localizes with γH2A.X in DNA damage-induced foci suggesting its function downstream of γH2A.X recognition. This along with tBRCT sequence similarities makes BCP1 functionally related to human PAXIP1. BCP1 and BCP4 are conserved in multicellular plants, and their evolution in Archaeplastida coincides with the acquisition of H2A.X in multicellular streptophytes. We conclude that BCP1 and BCP4 in plants and PAXIP1 and MDC1 in metazoa evolved independently from common ancestors with tBRCT domains.
Competing Interest Statement
The authors have declared no competing interest.