{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:40:56Z","timestamp":1791776456517,"version":"4.3.4"},"posted":{"date-parts":[[2026,4,1]]},"group-title":"Genomics","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["NIA R01 AG 067615"],"award-info":[{"award-number":["NIA R01 AG 067615"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NIGMS R35 118009"],"award-info":[{"award-number":["NIGMS R35 118009"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  DNA repair in biochemical and genetic experimental systems permits a precise definition of enzyme requirements and mechanistic steps. Comparing these findings to repair events at naturally occurring damage sites in multicellular organisms is essential for confirming and expanding these insights into a physiologic context. However, heterogeneity in any normal cell population increases with each cell division, and the reliable detection of replication-independent DNA damage sites and their repair has been a major barrier. Here, we examine single human colon crypts, which harbor natural cell clones, using a novel whole-genome sequencing (WGS) method to identify complex insertion-deletion (indel) in the crypt stem cells. Analysis of complex indel events likely repaired by non-homologous end joining occurring in crypt stem cells permits inferences about the\n                  <jats:italic>in vivo<\/jats:italic>\n                  repair of naturally occurring DNA damage within physiologically-relevant chromatin in normal human cells.\n                <\/jats:p>","DOI":"10.64898\/2026.03.30.714948","type":"posted-content","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T03:20:28Z","timestamp":1775100028000},"source":"Crossref","is-referenced-by-count":2,"title":["Fine Structural Features of Complex InDels and NHEJ Repair at Naturally Occurring Damage Sites in Normal Human Colon Crypts"],"prefix":"10.64898","author":[{"given":"Yong Hwee Eddie","family":"Loh","sequence":"first","affiliation":[{"name":"Norris Medical Library, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Lieber","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Okitsu","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Okitsu","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Wlodarczyk","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Southern California, Los Angeles, CA, USA; current affiliation: Intermountain Health Saint Joseph Hospital, Denver, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarko","family":"Manojlovic","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Lin","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040609500633000_2026.03.30.714948v2.1","doi-asserted-by":"crossref","unstructured":"Hsieh, C. L. , Z. Manojilovic , T. Okitsu , C. Okitsu , J. Wlodarczyk , N. Schillingford , R. Bawab , Y. E. Loh , and M. R. Lieber . 2025. Analysis of Naturally Occurring Somatic Insertions in the Human Genome. bioRxiv https:\/\/www.biorxiv.org\/cgi\/content\/short\/2025.09.24.677890v1.","DOI":"10.1101\/2025.09.24.677890"},{"key":"2026040609500633000_2026.03.30.714948v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00684-X"},{"key":"2026040609500633000_2026.03.30.714948v2.3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.pbiomolbio.2023.05.001","article-title":"The flexible and iterative steps within the NHEJ pathway","volume":"180-181","year":"2023","journal-title":"Prog Biophys Mol Biol"},{"key":"2026040609500633000_2026.03.30.714948v2.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.052308.093131"},{"key":"2026040609500633000_2026.03.30.714948v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00297-8"},{"key":"2026040609500633000_2026.03.30.714948v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00405-2"},{"key":"2026040609500633000_2026.03.30.714948v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.03.010"},{"key":"2026040609500633000_2026.03.30.714948v2.8","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11666"},{"key":"2026040609500633000_2026.03.30.714948v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.48"},{"key":"2026040609500633000_2026.03.30.714948v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.11.025"},{"key":"2026040609500633000_2026.03.30.714948v2.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1505805112"},{"key":"2026040609500633000_2026.03.30.714948v2.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2023.103491"},{"key":"2026040609500633000_2026.03.30.714948v2.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31365-6"},{"key":"2026040609500633000_2026.03.30.714948v2.14","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.6.3464"},{"key":"2026040609500633000_2026.03.30.714948v2.15","doi-asserted-by":"crossref","first-page":"11599","DOI":"10.1038\/s41467-025-66528-8","article-title":"Nonhomologous end-joining uses distinct mechanisms to repair each strand of a double strand break","volume":"16","year":"2025","journal-title":"Nat Commun"},{"key":"2026040609500633000_2026.03.30.714948v2.16","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-023-06333-y"},{"key":"2026040609500633000_2026.03.30.714948v2.17","doi-asserted-by":"crossref","unstructured":"Manojlovic, Z. , C. Okitsu , T. Okitsu , J. Wlodarczyk , M. R. Lieber , Y. E. Loh , and C. Hsieh . 2025. High-depth Whole Genome Sequencing of Single Human Colon Crypts Uncovers New View on Crypt Clonality. bioRxiv https:\/\/www.biorxiv.org\/cgi\/content\/short\/2025.09.24.677335v1.","DOI":"10.1101\/2025.09.24.677335"},{"key":"2026040609500633000_2026.03.30.714948v2.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.8356451"},{"key":"2026040609500633000_2026.03.30.714948v2.19","doi-asserted-by":"crossref","unstructured":"Duncan, J. R. , M. R. Lieber , N. Adachi , and R. Wahl . 2018. Radiation Dose Does Matter: Mechanistic Insights into DNA Damage and Repair Support the Linear No-Threshold Model of Low-Dose Radiation Health Risks. 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