Isolation and characterization of proteins cross-linked to DNA by the antitumor agent methylene dimethanesulfonate and its hydrolytic product formaldehyde.
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| Abstract |
This study attempted to characterize proteins cross-linked to DNA of Yoshida lymphosarcoma cells treated with methylene dimethanesulfonate (MDMS) and its hydrolytic products formaldehyde (HCHO) and methanesulfonic acid (MSA). MDMS and HCHO treatments produced a similar extent and type of DNA-protein cross-linking in Yoshida lymphosarcoma cells. All five major histones (H1, H2a, H2b, H3, and H4) were among the nuclear proteins cross-linked to DNA. Certain discrete differences were also apparent in these studies. MDMS cross-linked proteins of 29 and 48 kDa to DNA that were not observed following HCHO treatment alone, and HCHO cross-linked a 26-kDa protein to DNA that was not observed following MDMS treatment. Because semicarbazide prevented all MDMS-induced DNA-protein cross-linking, HCHO must be the component responsible for this lesion. The 26-kDa protein has been identified as an H4-H2b dimer. The formation of this dimer is particularly sensitive to MSA release on hydrolysis of MDMS because, in the presence of MSA, HCHO preferentially cross-linked an H2a-H2b dimer and a 48-kDa non-histone protein to DNA. Differences in DNA-protein cross-linking between these two agents are therefore proposed to arise from discrete changes in chromatin structure induced directly by MSA release.
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| Authors | P M O'Connor, B W Fox |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 264 Issue 11 Pg. 6391-7 (Apr 15 1989) ISSN: 0021-9258 [Print] United States |
| PMID | 2703496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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