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

Publication ,  Journal Article
Wakeman, TP; Wang, Q; Feng, J; Wang, X-F
Published in: EMBO J
May 2, 2012

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 a reduction in IR-induced 53BP1 foci formation, defects in DNA repair and increased sensitivity to IR. We demonstrate that a conserved Bat3 ubiquitin-like motif and a conserved DOT1L ubiquitin-interacting motif promote DOT1L-Bat3 interaction to facilitate efficient H3K79-2Me and IR-induced 53BP1 foci formation during G1/G2-phases. Taken together, our findings identify a novel role for Bat3 in regulating DOT1L function, which plays a critical role in DNA damage response.

Duke Scholars

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Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

May 2, 2012

Volume

31

Issue

9

Start / End Page

2169 / 2181

Location

England

Related Subject Headings

  • Tumor Suppressor p53-Binding Protein 1
  • Molecular Chaperones
  • Methyltransferases
  • Methylation
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Histones
  • Histone-Lysine N-Methyltransferase
  • Hela Cells
  • HeLa Cells
 

Citation

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Wakeman, T. P., Wang, Q., Feng, J., & Wang, X.-F. (2012). Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases. EMBO J, 31(9), 2169–2181. https://doi.org/10.1038/emboj.2012.50
Wakeman, Timothy P., Qinhong Wang, Junjie Feng, and Xiao-Fan Wang. “Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases.EMBO J 31, no. 9 (May 2, 2012): 2169–81. https://doi.org/10.1038/emboj.2012.50.
Wakeman, Timothy P., et al. “Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases.EMBO J, vol. 31, no. 9, May 2012, pp. 2169–81. Pubmed, doi:10.1038/emboj.2012.50.

Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

May 2, 2012

Volume

31

Issue

9

Start / End Page

2169 / 2181

Location

England

Related Subject Headings

  • Tumor Suppressor p53-Binding Protein 1
  • Molecular Chaperones
  • Methyltransferases
  • Methylation
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Histones
  • Histone-Lysine N-Methyltransferase
  • Hela Cells
  • HeLa Cells