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During regeneration, the blastema cells accelerate the cell cycle and duplicate its genome, which is inherently difficult to replicate because of its length and composition, thus being prone to suffer double\u2010strand breaks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified and characterized two remarkable components of the homologous recombination repair pathway (Amex.RAD51 and Amex.MRE11), which were heterologously expressed, biochemically characterized, and inhibited by specific chemicals. These same inhibitors were applied at different time points after amputation to study their effects during limb regeneration. We observed an increase in cellular senescent accompanied by a slight delay in regeneration at 28\u2009days postamputation regenerated tissues; moreover, inhibitors caused a rise in the double\u2010strand break signaling as a response to the inhibition of the repair mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We confirmed the participation and importance of homologous recombination during limb regeneration. The chemical inhibition induces double\u2010strand breaks that lead to DNA damage associated senescence, or in an alternatively way, this damage could be possibly repaired by a different DNA repair pathway, permitting proper regeneration and avoiding senescence.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.455","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T05:44:21Z","timestamp":1642484661000},"page":"1035-1053","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evidence of requirement for homologous\u2010mediated <scp>DNA<\/scp> repair during <i>Ambystoma mexicanum<\/i> limb regeneration"],"prefix":"10.1002","volume":"251","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4808-9441","authenticated-orcid":false,"given":"Ulises Omar","family":"Garc\u00eda\u2010Lepe","sequence":"first","affiliation":[{"name":"Genetics and Molecular Biology Department Centro de Investigaci\u00f3n y Estudios Avanzados del IPN  Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Torres\u2010Dimas","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Department Centro de Investigaci\u00f3n y Estudios Avanzados del IPN  Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Espinal\u2010Centeno","sequence":"additional","affiliation":[{"name":"Molecular and Developmental Complexity Group Unidad de Gen\u00f3mica Avanzada (LANGEBIO), Centro de Investigaci\u00f3n y de Estudios Avanzados del IPN  Guanajuato Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Cruz\u2010Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Molecular and Developmental Complexity Group Unidad de Gen\u00f3mica Avanzada (LANGEBIO), Centro de Investigaci\u00f3n y de Estudios Avanzados del IPN  Guanajuato Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0463-9357","authenticated-orcid":false,"given":"Rosa Mar\u00eda","family":"Berm\u00fadez\u2010Cruz","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Department Centro de Investigaci\u00f3n y Estudios Avanzados del IPN  Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20102495\u20100_3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.038"},{"key":"e_1_2_8_4_1","first-page":"68","volume-title":"Reproductions of the legs in the aquatic salamander. 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