{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:33:11Z","timestamp":1788985991177,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2047553"],"award-info":[{"award-number":["2047553"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2047553"],"award-info":[{"award-number":["2047553"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institutes of Health of General Medical Sciences","award":["P20GM103427"],"award-info":[{"award-number":["P20GM103427"]}]},{"name":"National Institutes of Health of General Medical Sciences","award":["R35GM142784"],"award-info":[{"award-number":["R35GM142784"]}]},{"DOI":"10.13039\/100000057","name":"Nebraska Center for Integrated Biomolecular Communication","doi-asserted-by":"publisher","award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}],"id":[{"id":"https:\/\/ror.org\/02vajdy81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Proliferating cell nuclear antigen (PCNA) is an essential sliding clamp that coordinates nearly all DNA-templated processes. It does so by recruiting a diverse array of factors to DNA through PCNA-interacting protein (PIP) motifs on PCNA-binding proteins. Chromatin assembly factor 1 (CAF-1) is a histone chaperone that deposits histones onto silent regions of the genome immediately following DNA replication. PCNA recruitment of CAF-1 to the replication fork is essential for nucleosome assembly and epigenetic inheritance. In yeast, CAF-1 recruitment to PCNA is assumed to be facilitated using one PIP motif. Here, we identify a second PIP motif in CAF-1, designated PIP1, located within the N-terminal intrinsically disordered region of the protein. Binding kinetics demonstrate that the PIP1 motif sequence binds PCNA with substantially lower affinity than the previously characterized PIP motif, designated PIP2. Structural and binding data reveal PIP1 as an extended PIP motif, in which C-terminal flanking residues make extensive, atypical contacts with PCNA that significantly increase its affinity. Neither PIP1 nor PIP2 alone is required for CAF-1\u2013mediated gene silencing in vivo, but simultaneous disruption of both abolishes CAF-1 function. Together, these findings suggest CAF-1 engages PCNA multivalently and provide new insight into how PCNA selectively recognizes binding partners during nucleosome assembly.<\/jats:p>","DOI":"10.3390\/biom16091274","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:10:33Z","timestamp":1788430233000},"page":"1274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of a Second PIP Motif Reveals New Insights into PCNA Recognition by Yeast CAF-1"],"prefix":"10.3390","volume":"16","author":[{"given":"Ian","family":"Hall","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Iain M.","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Stephanie A.","family":"Limaye","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ivy L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Cael E.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8046-4719","authenticated-orcid":false,"given":"Trevor J.","family":"Snetsinger","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Andy E.","family":"Agbakpo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-6163","authenticated-orcid":false,"given":"James W.","family":"Checco","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"},{"name":"Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1532-0897","authenticated-orcid":false,"given":"Lynne M.","family":"Dieckman","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.molcel.2016.12.020","article-title":"Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork","volume":"65","author":"Choe","year":"2017","journal-title":"Mol. 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