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In this study, we investigated the mechanism of recognition and repair of protein\u2013DNA and oligopeptide\u2013DNA crosslinks by the human excision nuclease. Under our assay conditions, the human nucleotide excision repair system did not remove a 16-kDa protein crosslinked to DNA at a detectable level. However, 4- and 12-aa-long oligopeptides crosslinked to the DNA backbone were recognized by some of the damage recognition factors of the human excision nuclease with moderate selectivity and were excised from DNA at relatively efficient rates. Our data suggest that, if coupled with proteolytic degradation of the crosslinked protein, the human excision nuclease may be the major enzyme system for eliminating protein\u2013DNA crosslinks from the genome.<\/jats:p>","DOI":"10.1073\/pnas.0600538103","type":"journal-article","created":{"date-parts":[[2006,3,6]],"date-time":"2006-03-06T20:34:02Z","timestamp":1141677242000},"page":"4056-4061","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":86,"title":["Repair of DNA\u2013polypeptide crosslinks by human excision nuclease"],"prefix":"10.1073","volume":"103","author":[{"given":"Joyce T.","family":"Reardon","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Sancar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,3,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11534"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508898200"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.552"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03872"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2004.11.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1987.28"},{"key":"e_1_3_3_7_2","first-page":"365","volume":"39","author":"Zwelling L. 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