{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:34Z","timestamp":1791417634926,"version":"4.3.3"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T00:00:00Z","timestamp":1545868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P01 GM105473"],"award-info":[{"award-number":["P01 GM105473"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM007122"],"award-info":[{"award-number":["T32 GM007122"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Covalent DNA protein crosslinks (DPCs) are common lesions that block replication. We examine here the consequence of DPCs on mutagenesis involving replicational template-switch reactions in Escherichia coli. 5-Azacytidine (5-azaC) is a potent mutagen for template-switching. This effect is dependent on DNA cytosine methylase (Dcm), implicating the Dcm-DNA covalent complex trapped by 5-azaC as the initiator for mutagenesis. The leading strand of replication is more mutable than the lagging strand, which can be explained by blocks to the replicative helicase and\/or fork regression. We find that template-switch mutagenesis induced by 5-azaC does not require double strand break repair via RecABCD; the ability to induce the SOS response is anti-mutagenic. Mutants in recB, but not recA, exhibit high constitutive rates of template-switching, and we suggest that RecBCD-mediated DNA degradation prevents template-switching associated with fork regression. A mutation in the DnaB fork helicase also promotes high levels of template-switching. We also find that other DPC-inducers, formaldehyde (a non-specific crosslinker) and ciprofloxacin (a topoisomerase II poison) are also strong mutagens for template-switching with similar genetic properties. Induction of mutations and genetic rearrangements that occur by template-switching may constitute a previously unrecognized component of the genotoxicity and genetic instability promoted by DPCs.<\/jats:p>","DOI":"10.3390\/genes10010014","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T11:29:43Z","timestamp":1545910183000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Stimulation of Replication Template-Switching by DNA-Protein Crosslinks"],"prefix":"10.3390","volume":"10","author":[{"given":"Laura T.","family":"Laranjo","sequence":"first","affiliation":[{"name":"Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454-9110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Klaric","sequence":"additional","affiliation":[{"name":"Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454-9110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah R.","family":"Pearlman","sequence":"additional","affiliation":[{"name":"Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454-9110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2792-1857","authenticated-orcid":false,"given":"Susan T.","family":"Lovett","sequence":"additional","affiliation":[{"name":"Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454-9110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/35003501","article-title":"The importance of repairing stalled replication forks","volume":"404","author":"Cox","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.mrrev.2004.11.003","article-title":"DNA-protein crosslinks: Their induction, repair, and biological consequences","volume":"589","author":"Barker","year":"2005","journal-title":"Mutat. 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