{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:49:58Z","timestamp":1782280198505,"version":"3.54.5"},"posted":{"date-parts":[[2025,4,7]]},"group-title":"Microbiology","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["R01AI146153"],"award-info":[{"award-number":["R01AI146153"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The haploid malaria parasite,\n                  <jats:italic>Plasmodium falciparum,<\/jats:italic>\n                  evolved a unique cohort of DNA repair pathways enabling the parasite to survive in a vertebrate host red blood cell and the mosquito vector.\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  chromosomes are partitioned into a highly conserved core genome and remarkably diverse, largely subtelomeric regions that contain genes encoding important parasite virulence factors. The molecular mechanisms that maintain this chromosomal structure have not been identified. Here, we describe specific DNA repair pathways that differentiate between hypervariable subtelomeric and conserved core regions of the genome. Based on our previous work, we hypothesized that there are potentially important interactions between translesion (TLS) and homologous recombination (HR) pathways for the diversification of multicopy gene families in\n                  <jats:italic>P. falciparum.<\/jats:italic>\n                  Thus, we created knockout parasite lines of the DNA repair enzymes:\n                  <jats:italic>PfRad51<\/jats:italic>\n                  and the TLS polymerases\n                  <jats:italic>PfPol<\/jats:italic>\n                  \u03b6 and\n                  <jats:italic>PfRev1<\/jats:italic>\n                  . We identified that irradiation hypersensitivity varied across the cell cycle for TLS\u0394 parasites and was uniform across the erythrocytic cycle for\n                  <jats:italic>PfRad51<\/jats:italic>\n                  \u0394 parasites, highlighting the variable roles of these pathways. However, important interactions between these pathways were found when we studied directed double strand break (DSB) repair, which revealed a difference in the DNA damage response according to chromosomal location.\n                  <jats:italic>PfRad51<\/jats:italic>\n                  was essential for HR-mediated repair in the core genome. In contrast, we identified a Rad51 independent homology-directed repair in all three of our knockout lines when a DSB was made in the subtelomeric region of the chromosome. We propose that this differential DNA damage response maintains the distinction in diversification across the chromosome.\n                <\/jats:p>","DOI":"10.1101\/2025.04.07.647301","type":"posted-content","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:50:26Z","timestamp":1744073426000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Plasmodium falciparum<\/i>\n                  DNA repair dynamics reveal unique roles for TLS polymerases and PfRad51 in genome diversification"],"prefix":"10.64898","author":[{"given":"Akshay","family":"Vishwanatha","sequence":"first","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi 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