HMGB1 Is a Cofactor in Mammalian Base Excision Repair Article

Prasad, R, Liu, Y, Deterding, LJ et al. (2007). HMGB1 Is a Cofactor in Mammalian Base Excision Repair . 27(5), 829-841. 10.1016/j.molcel.2007.06.029

cited authors

  • Prasad, R; Liu, Y; Deterding, LJ; Poltoratsky, VP; Kedar, PS; Horton, JK; Kanno, SI; Asagoshi, K; Hou, EW; Khodyreva, SN; Lavrik, OI; Tomer, KB; Yasui, A; Wilson, SH

authors

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. © 2007 Elsevier Inc. All rights reserved.

publication date

  • September 7, 2007

Digital Object Identifier (DOI)

start page

  • 829

end page

  • 841

volume

  • 27

issue

  • 5