{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:05:37Z","timestamp":1779213937742,"version":"3.51.4"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":64,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01DK127738"],"award-info":[{"award-number":["R01DK127738"]}]},{"name":"NIH","award":["R01HL095675"],"award-info":[{"award-number":["R01HL095675"]}]},{"name":"NIH","award":["T32 DK007780"],"award-info":[{"award-number":["T32 DK007780"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["TL1DK143326"],"award-info":[{"award-number":["TL1DK143326"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:p>\n                    The adaptor protein LNK\/SH2B3 negatively regulates hematopoietic stem cell (HSC) homeostasis.\n                    <jats:italic>Lnk-<\/jats:italic>\n                    deficient mice show marked expansion of HSCs without premature exhaustion.\n                    <jats:italic>Lnk<\/jats:italic>\n                    deficiency largely restores HSC function in Fanconi anemia (FA) mouse models and primary FA patient cells, albeit protective mechanisms remain enigmatic. Here, we uncover a role for LNK in regulating translesion synthesis (TLS) during HSC replication.\n                    <jats:italic>Lnk<\/jats:italic>\n                    deficiency reduced replication stress\u2013associated DNA damage, particularly in the FA background.\n                    <jats:italic>Lnk<\/jats:italic>\n                    deficiency suppressed single-strand DNA breaks, while enhancing replication fork restart in FA-deficient HSCs. Diminished replication-associated damage in\n                    <jats:italic>Lnk<\/jats:italic>\n                    -deficient HSCs occurred commensurate with reduced ATR\/p53 checkpoint activation that is linked to HSC attrition. Notably,\n                    <jats:italic>Lnk<\/jats:italic>\n                    deficiency ameliorated HSC attrition in FA mice without exacerbating carcinogenesis during aging. Moreover, we demonstrated that enhanced HSC fitness from\n                    <jats:italic>Lnk<\/jats:italic>\n                    deficiency was associated with increased TLS activity via REV1 and, to a lesser extent, TLS polymerase eta (\u03b7). TLS polymerases are specialized to execute DNA replication in the presence of lesions or natural replication fork barriers that stall replicative polymerases. Our findings implicate elevated use of these specialized DNA polymerases as critical to the enhanced HSC function imparted by\n                    <jats:italic>Lnk<\/jats:italic>\n                    deficiency, which has important ramifications for stem cell therapy and regenerative medicine in general.\n                  <\/jats:p>","DOI":"10.1172\/jci191713","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T16:00:17Z","timestamp":1761840017000},"source":"Crossref","is-referenced-by-count":0,"title":["Lnk deficiency enhances translesion synthesis to alleviate replication stress and promote hematopoietic stem cell fitness"],"prefix":"10.1172","volume":"136","author":[{"given":"Brijendra","family":"Singh","sequence":"first","affiliation":[{"name":"Division of Hematology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."},{"name":"Division of Pediatrics and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md 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