Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases.

ABSTRACT: The methyltransferase DOT1L methylates histone H3 at K79 to facilitate specific biological events. H3K79 dimethylation (H3K79-2Me) by DOT1L influences the DNA damage response by promoting 53BP1 recruitment to DNA damage sites; however, it is unclear if this methylation is required as 53BP1 interacts with dimethylated H4 (H4K20-2Me) with a much higher affinity. We demonstrate that H3K79-2Me, while negligible during S-phase, is required for ionizing radiation (IR)-induced 53BP1 foci formation during G1/G2-phases when H4K20-2Me levels are low. Further, we describe an essential role for HLA-B-associated transcript 3 (Bat3) in regulating this process in U2OS cells. Bat3 co-localizes with DOT1L at histone H3, and Bat3 knockdown results in decreased DOT1L-H3 interaction and H3K79-2Me, leading to

SUBMITTER: Wakeman TP 

PROVIDER: S-EPMC3343460 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature