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Physiol."],"abstract":"<jats:p>Cleft palate is one of the most common craniofacial birth defects, however, little is known about how changes in the DNA damage response (DDR) cause cleft palate. To determine the role of DDR during palatogenesis, the DDR process was altered using a pharmacological intervention approach. A compromised DDR caused by a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor resulted in cleft palate in wild-type mouse embryos, with increased DNA damage and apoptosis. In addition, a mouse genetic approach was employed to disrupt breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2), known as key players in DDR. An ectomesenchymal-specific deletion of<jats:italic>Brca1<\/jats:italic>or<jats:italic>Brca2<\/jats:italic>resulted in cleft palate due to attenuation of cell survival. This was supported by the phenotypes of the ectomesenchymal-specific<jats:italic>Brca1<\/jats:italic>\/<jats:italic>Brca2<\/jats:italic>double-knockout mice. The cleft palate phenotype was rescued by superimposing p53 null alleles, demonstrating that the BRCA1\/2\u2013p53 DDR pathway is critical for palatogenesis. Our study highlights the importance of DDR in palatogenesis.<\/jats:p>","DOI":"10.3389\/fphys.2021.649492","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T05:29:45Z","timestamp":1616995785000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Alteration of DNA Damage Response Causes Cleft Palate"],"prefix":"10.3389","volume":"12","author":[{"given":"Hiroyuki","family":"Yamaguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Kitami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.ydbio.2011.12.042","article-title":"Development and evolution of the neural crest: an overview.","volume":"366","author":"Bronner","year":"2012","journal-title":"Dev. 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