HMGB1 Is a Cofactor in Mammalian Base Excision Repair

Rajendra Prasad, Yuan Liu, Leesa J. Deterding, Vladimir P. Poltoratsky, Padmini S. Kedar, Julie K. Horton, Shin Ichiro Kanno, Kenjiro Asagoshi, Esther W. Hou, Svetlana N. Khodyreva, Olga I. Lavrik, Kenneth B. Tomer, Akira Yasui, Samuel H. Wilson

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

Abstract

Deoxyribose phosphate (dRP) removal by DNA polymerase β (Pol β) is a pivotal step in base excision repair (BER). To identify BER cofactors, especially those with dRP lyase activity, we used a Pol β null cell extract and BER intermediate as bait for sodium borohydride crosslinking. Mass spectrometry identified the high-mobility group box 1 protein (HMGB1) as specifically interacting with the BER intermediate. Purified HMGB1 was found to have weak dRP lyase activity and to stimulate AP endonuclease and FEN1 activities on BER substrates. Coimmunoprecipitation experiments revealed interactions of HMGB1 with known BER enzymes, and GFP-tagged HMGB1 was found to accumulate at sites of oxidative DNA damage in living cells. HMGB1-/- mouse cells were slightly more resistant to MMS than wild-type cells, probably due to the production of fewer strand-break BER intermediates. The results suggest HMGB1 is a BER cofactor capable of modulating BER capacity in cells.

Original languageEnglish
Pages (from-to)829-841
Number of pages13
JournalMolecular Cell
Volume27
Issue number5
DOIs
Publication statusPublished - 2007 Sep 7

Keywords

  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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