{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:26:49Z","timestamp":1781108809158,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,1,9]]},"abstract":"<jats:p>High-density mutational spectra have been established for exon 3 of the gene encoding adenine phosphoribosyltransferase (APRT) of the Chinese hamster ovary (CHO) cell line derivative D422 and closely related and\/or modified lines by using the mutagen ethyl methanesulfonate (EMS). The total number of selectable sites (GC--&gt;AT transitions yielding a selectable APRT- phenotype) was estimated at 31 based on our own accumulated data base of 136 sequenced exon 3 mutations and on literature reports. D422 and two other APRT hemizygous lines each yielded very similar spectra and showed two populations of mutable sites: (i) 24 \"baseline\" sites that followed the Poisson distribution and therefore were equally susceptible to mutation and (ii) two hotspots, one comprising a cluster at nucleotides 1293-1309 and the other at nucleotide 1365. Collectively, the latter sites were about 10-fold more frequently mutated than the others. CHO cells are mer- as they lack the repair enzyme O6-methylguanidine methyltransferase (EC 2.1.1.63). In modified repair-proficient CHO cells, the distribution of mutations among all of the 31 sites was random, with only 3 of the 19 GC--&gt;AT transitions in the above hotspots. To determine whether the distribution was locus-dependent, two independent lines carrying single copies of transfected APRT genes were generated from a derivative of D422 carrying a deletion in the endogenous APRT gene. Nucleotides 1293-1309 were again no longer preferentially mutated, but the site at nucleotide 1365 was still a hotspot. We conclude that mutational spectra in mer- cells are at least in part locus dependent and that some sequences are particularly susceptible to EMS mutagenesis and perhaps also to methyltransferase repair.<\/jats:p>","DOI":"10.1073\/pnas.93.1.121","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:43:20Z","timestamp":1027680200000},"page":"121-125","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Influence of alkyltransferase activity and chromosomal locus on mutational hotspots in Chinese hamster ovary cells."],"prefix":"10.1073","volume":"93","author":[{"given":"A","family":"Belouchi","sequence":"first","affiliation":[{"name":"Institut du cancer de Montr\u00e9al, Centre de Recherche Louis-Charles Simard, Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Ouimet","sequence":"additional","affiliation":[{"name":"Institut du cancer de Montr\u00e9al, Centre de Recherche Louis-Charles Simard, Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Dion","sequence":"additional","affiliation":[{"name":"Institut du cancer de Montr\u00e9al, Centre de Recherche Louis-Charles Simard, Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Gaudreault","sequence":"additional","affiliation":[{"name":"Institut du cancer de Montr\u00e9al, Centre de Recherche Louis-Charles Simard, Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W E","family":"Bradley","sequence":"additional","affiliation":[{"name":"Institut du cancer de Montr\u00e9al, Centre de Recherche Louis-Charles Simard, Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,1,9]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.1.121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:11:36Z","timestamp":1649859096000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.1.121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,1,9]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1996,1,9]]}},"alternative-id":["10.1073\/pnas.93.1.121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.1.121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,1,9]]},"assertion":[{"value":"1996-01-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}