{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:43:51Z","timestamp":1790257431423,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,8,11]],"date-time":"2006-08-11T00:00:00Z","timestamp":1155254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Concurrent activation of poly (ADP\u2010ribose) polymerase (PARP) and DNA ligase was observed in cultured human epidermal keratinocytes (HEK) exposed to the DNA alkylating compound sulfur mustard (SM), suggesting that DNA ligase activation could be due to its modification by PARP. Using HEK, intracellular <jats:sup>3<\/jats:sup>H\u2010labeled NAD<jats:sup>+<\/jats:sup> (<jats:sup>3<\/jats:sup>H\u2010adenine) was metabolically generated and then these cells were exposed to SM (1 m<jats:sc>M<\/jats:sc>). DNA ligase I isolated from these cells was not <jats:sup>3<\/jats:sup>H\u2010labeled, indicating that DNA ligase I is not a substrate for (ADP\u2010ribosyl)ation by PARP. In HEK, when PARP was inhibited by 3\u2010amino benzamide (3\u2010AB, 2 m<jats:sc>M<\/jats:sc>), SM\u2010activated DNA ligase had a half\u2010life that was four\u2010fold higher than that observed in the absence of 3\u2010AB. These results suggest that DNA repair requires PARP, and that DNA ligase remains activated until DNA damage repair is complete. The results show that in SM\u2010exposed HEK, DNA ligase I is activated by phosphorylation catalysed by DNA\u2010dependent protein kinase (DNA\u2010PK). Therefore, the role of PARP in DNA repair is other than that of DNA ligase I activation. By using the DNA ligase I phosphorylation assay and decreasing PARP chemically as well as by PARP anti\u2010sense mRNA expression in the cells, it was confirmed that PARP does not modify DNA ligase I. In conclusion, it is proposed that PARP is essential for efficient DNA repair; however, PARP participates in DNA repair by altering the chromosomal structure to make the DNA damage site(s) accessible to the repair enzymes. Published in 2006 by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1161","type":"journal-article","created":{"date-parts":[[2006,8,11]],"date-time":"2006-08-11T10:16:26Z","timestamp":1155291386000},"page":"452-457","source":"Crossref","is-referenced-by-count":22,"title":["Poly (ADP\u2010ribose) polymerase (PARP) is essential for sulfur mustard\u2010induced DNA damage repair, but has no role in DNA ligase activation"],"prefix":"10.1002","volume":"26","author":[{"given":"K. Ramachandra","family":"Bhat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty J.","family":"Benton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radharaman","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,8,11]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404524200"},{"key":"e_1_2_1_3_1","first-page":"45","article-title":"DNA ligase activation following sulfur mustard exposure in cultured human epidermal keratinocytes","volume":"11","author":"Bhat KR","year":"1998","journal-title":"In Vitro Mol. 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