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Histone lysines are another source of aldehyde\u2010reactive amino groups in chromatin, however, chromatin\/histone damage responses to FA and their biological significance are poorly understood. We examined histone posttranslational modifications in FA\u2010treated human lung cells and found that the majority of the most prominent small lysine modifications associated with active or inactive chromatin were unchanged. FA moderately decreased H3K9 and H3K27 acetylation and H2A\u2010K119 monoubiquitination but caused surprisingly severe losses of H2B\u2010K120 monoubiquitination, especially in primary and stem\u2010like cells. H2Aub1 decreases reflected its slower ubiquitination linked to a lower ubiquitin availability due to K48\u2010polyubiquitination of FA\u2010damaged proteins. Depletion of H2Bub1 resulted from its rapid deubiquitination in part by ATXN7L3\u2010associated deubiquitinases and was independent on DNA damage signaling, indicating a direct chromatin damage response. Manipulations of H2Bub1 abundance showed that it was important for robust ATM and ATR signaling, efficient S\u2010phase checkpoint, and suppression of mitotic transmission of unreplicated DNA and formation of micronuclei. Our findings identified H2B deubiquitination as a major FA\u2010induced chromatin damage response that regulates S\u2010phase checkpoint signaling and genome stability.<\/jats:p>","DOI":"10.1002\/mc.23819","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T13:55:53Z","timestamp":1725976553000},"page":"2414-2424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Monoubiquitinated H2B, a Main Chromatin Target of Formaldehyde, Is Important for S\u2010Phase Checkpoint Signaling and Genome Stability"],"prefix":"10.1002","volume":"63","author":[{"given":"Sasmita","family":"Mishra","sequence":"first","affiliation":[{"name":"Department Pathology and Laboratory Medicine Brown University Providence Rhode Island USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey","family":"Krawic","sequence":"additional","affiliation":[{"name":"Department Pathology and Laboratory 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