Skip to main content

Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks.

Publication ,  Journal Article
Bekker-Jensen, S; Lukas, C; Kitagawa, R; Melander, F; Kastan, MB; Bartek, J; Lukas, J
Published in: J Cell Biol
April 24, 2006

We show that DNA double-strand breaks (DSBs) induce complex subcompartmentalization of genome surveillance regulators. Chromatin marked by gamma-H2AX is occupied by ataxia telangiectasia-mutated (ATM) kinase, Mdc1, and 53BP1. In contrast, repair factors (Rad51, Rad52, BRCA2, and FANCD2), ATM and Rad-3-related (ATR) cascade (ATR, ATR interacting protein, and replication protein A), and the DNA clamp (Rad17 and -9) accumulate in subchromatin microcompartments delineated by single-stranded DNA (ssDNA). BRCA1 and the Mre11-Rad50-Nbs1 complex interact with both of these compartments. Importantly, some core DSB regulators do not form cytologically discernible foci. These are further subclassified to proteins that connect DSBs with the rest of the nucleus (Chk1 and -2), that assemble at unprocessed DSBs (DNA-PK/Ku70), and that exist on chromatin as preassembled complexes but become locally modified after DNA damage (Smc1/Smc3). Finally, checkpoint effectors such as p53 and Cdc25A do not accumulate at DSBs at all. We propose that subclassification of DSB regulators according to their residence sites provides a useful framework for understanding their involvement in diverse processes of genome surveillance.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Cell Biol

DOI

ISSN

0021-9525

Publication Date

April 24, 2006

Volume

173

Issue

2

Start / End Page

195 / 206

Location

United States

Related Subject Headings

  • Protein Kinases
  • Phosphorylation
  • Nuclear Proteins
  • Lasers
  • Humans
  • Genome
  • Developmental Biology
  • DNA Repair
  • DNA Damage
  • DNA
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bekker-Jensen, S., Lukas, C., Kitagawa, R., Melander, F., Kastan, M. B., Bartek, J., & Lukas, J. (2006). Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J Cell Biol, 173(2), 195–206. https://doi.org/10.1083/jcb.200510130
Bekker-Jensen, Simon, Claudia Lukas, Risa Kitagawa, Fredrik Melander, Michael B. Kastan, Jiri Bartek, and Jiri Lukas. “Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks.J Cell Biol 173, no. 2 (April 24, 2006): 195–206. https://doi.org/10.1083/jcb.200510130.
Bekker-Jensen S, Lukas C, Kitagawa R, Melander F, Kastan MB, Bartek J, et al. Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J Cell Biol. 2006 Apr 24;173(2):195–206.
Bekker-Jensen, Simon, et al. “Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks.J Cell Biol, vol. 173, no. 2, Apr. 2006, pp. 195–206. Pubmed, doi:10.1083/jcb.200510130.
Bekker-Jensen S, Lukas C, Kitagawa R, Melander F, Kastan MB, Bartek J, Lukas J. Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J Cell Biol. 2006 Apr 24;173(2):195–206.

Published In

J Cell Biol

DOI

ISSN

0021-9525

Publication Date

April 24, 2006

Volume

173

Issue

2

Start / End Page

195 / 206

Location

United States

Related Subject Headings

  • Protein Kinases
  • Phosphorylation
  • Nuclear Proteins
  • Lasers
  • Humans
  • Genome
  • Developmental Biology
  • DNA Repair
  • DNA Damage
  • DNA