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

doi:10.1016/j.molcel.2007.06.029

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

Division of Cancer Science

Research output: Contribution to journal › Article › peer-review

127 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 language	English
Pages (from-to)	829-841
Number of pages	13
Journal	Molecular Cell
Volume	27
Issue number	5
DOIs	https://doi.org/10.1016/j.molcel.2007.06.029
Publication status	Published - 2007 Sept 7

Keywords

RNA

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2007.06.029

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@article{77f626591a82408bb0ddf2e81420f143,

title = "HMGB1 Is a Cofactor in Mammalian Base Excision Repair",

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.",

keywords = "RNA",

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

note = "Funding Information: This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, and in part by a genome network project grant from the Ministry of Education, Science, Sports, and Culture of Japan (to A.Y.). We thank Dr. Jack A. Taylor, National Institute of Environmental Health Sciences/National Institutes of Health, for providing the scoring system for comet assay and Dr. William A. Beard for critical discussions and help with figure preparation. We also thank Jennifer Myers for editorial assistance and Zachary Weiner and Mikiko Hoshi for technical assistance. ",

year = "2007",

month = sep,

day = "7",

doi = "10.1016/j.molcel.2007.06.029",

language = "English",

volume = "27",

pages = "829--841",

journal = "Molecular Cell",

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T1 - HMGB1 Is a Cofactor in Mammalian Base Excision Repair

AU - Prasad, Rajendra

AU - Liu, Yuan

AU - Deterding, Leesa J.

AU - Poltoratsky, Vladimir P.

AU - Kedar, Padmini S.

AU - Horton, Julie K.

AU - Kanno, Shin Ichiro

AU - Asagoshi, Kenjiro

AU - Hou, Esther W.

AU - Khodyreva, Svetlana N.

AU - Lavrik, Olga I.

AU - Tomer, Kenneth B.

AU - Yasui, Akira

AU - Wilson, Samuel H.

N1 - Funding Information: This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, and in part by a genome network project grant from the Ministry of Education, Science, Sports, and Culture of Japan (to A.Y.). We thank Dr. Jack A. Taylor, National Institute of Environmental Health Sciences/National Institutes of Health, for providing the scoring system for comet assay and Dr. William A. Beard for critical discussions and help with figure preparation. We also thank Jennifer Myers for editorial assistance and Zachary Weiner and Mikiko Hoshi for technical assistance.

PY - 2007/9/7

Y1 - 2007/9/7

N2 - 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.

AB - 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.

KW - RNA

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SN - 1097-2765

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JO - Molecular Cell

JF - Molecular Cell

IS - 5

ER -

HMGB1 Is a Cofactor in Mammalian Base Excision Repair

Abstract

Keywords

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