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Little is known about the Leishmania RSR. Here, we reveal the global dynamics of the RSR in Leishmania major by performing ChIP-seq, focusing on two key RSR proteins, \u03b3H2A and RPA1, in the absence and presence of RS. We show that common RS \u2018hotspots\u2019 coincide with DNA replication initiation and transcription termination in Leishmania. When replication is stalled, RSR factors accumulate at early S-phase origins, with a signal pattern reminiscent of bidirectional RF progression. Under chronic RS conditions, increased accumulation of RSR factors emerges at wider sites of transcription initiation, suggesting Leishmania may possess compensatory strategies to limit the effects of RS and ensure DNA replication completion under stress. In contrast, chronic RS enhances RSR factor accumulation at transcription termination sites, highlighting these regions as RS \u2018hotspots\u2019 in Leishmania. Lastly, variations in replication protein A (RPA) dynamics in Ataxia Telangiectasia and Rad3 Related (ATR)-deficient cells uncover crucial roles of this kinase in managing polycistronic transcription and DNA replication, particularly under RS, in Leishmania.<\/jats:p>","DOI":"10.1093\/nar\/gkag754","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:06:06Z","timestamp":1784721966000},"source":"Crossref","is-referenced-by-count":0,"title":["Genome-wide mapping of replication stress response factors reveals the management of polycistronic transcription, replication initiation, and responses to replication stress in\n                    <i>Leishmania<\/i>"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5219-3172","authenticated-orcid":false,"given":"Jennifer A","family":"Black","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, 14040-900 SP,","place":["Brazil"]},{"name":"University of Glasgow Centre for Parasitology, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stela","family":"Virgilio","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, 14040-900 SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus S","family":"Bastos","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, 14040-900 SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel L A","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, 14040-900 SP,","place":["Brazil"]},{"name":"University of Glasgow Centre for Parasitology, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-3214","authenticated-orcid":false,"given":"Jeziel\u00a0D","family":"Damasceno","sequence":"additional","affiliation":[{"name":"University of Glasgow Centre for Parasitology, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9310-4762","authenticated-orcid":false,"given":"Kathryn","family":"Crouch","sequence":"additional","affiliation":[{"name":"University of Glasgow Centre for Parasitology, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Lapsley","sequence":"additional","affiliation":[{"name":"University of Glasgow Centre for Parasitology, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-976X","authenticated-orcid":false,"given":"Richard","family":"McCulloch","sequence":"additional","affiliation":[{"name":"University of Glasgow Centre for Parasitology, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9932-5486","authenticated-orcid":false,"given":"Luiz\u00a0R O","family":"Tosi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, 14040-900 SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"2026081006234325700_B1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1146\/annurev-biochem-072321-110228","article-title":"The initiation of eukaryotic DNA replication","volume":"91","author":"Costa","year":"2022","journal-title":"Annu Rev 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