Fixing Broken DNA

Sci. Signal., 12 February 2013
Vol. 6, Issue 262, p. ec42
DOI: 10.1126/scisignal.2004047

Fixing Broken DNA

  1. Kristen L. Mueller
  1. Science Signaling, AAAS, Washington, DC 20005, USA

Some physiological processes, such as immunoglobulin class switching and telomere attrition, result in double-stranded DNA breaks. The DNA damage repair protein, 53BP1, prevents nucleolytic processing of these breaks, but the proteins it partners with to do this are unknown (see the Perspective by Lukas and Lukas). Di Virgilio et al., using mass spectroscopy–based methods, and Zimmermann et al., using a telomere-based assay, identify Rif1 as a 53BP1 phosphorylation- and DNA damage–dependent interaction partner. Mice with a B cell–specific deletion in Rif1 showed impaired immunoglobulin class switching. Rif1-deficient cells exhibited extensive 5′-3′ resection at DNA ends, with enhanced genetic instability. Thus, Rif1 partners with 53BP1 to promote the proper repair of double-stranded DNA breaks.

M. Zimmermann, F. Lottersberger, S. B. Buonomo, A. Sfeir, T. de Lange, 53BP1 regulates DSB repair using Rif1 to control 5′ end resection. Science 339, 700–704 (2013). [Abstract] [Full Text]

M. Di Virgilio, E. Callen, A. Yamane, W. Zhang, M. Jankovic, A. D. Gitlin, N. Feldhahn, W. Resch, T. Y. Oliveira, B. T. Chait, A. Nussenzweig, R. Casellas, D. F. Robbiani, M. C. Nussenzweig, Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339, 711–715 (2013). [Abstract] [Full Text]

J. Lukas, C. Lukas, Shielding broken DNA for a quick fix. Science 339, 652–653 (2013). [Abstract] [Full Text]


K. L. Mueller, Fixing Broken DNA. Sci. Signal. 6, ec42 (2013).
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