PMID- 38526189 OWN - NLM STAT- MEDLINE DCOM- 20240409 LR - 20240425 IS - 2046-6390 (Electronic) IS - 2046-6390 (Linking) VI - 13 IP - 4 DP - 2024 Apr 15 TI - Cdc48 and its co-factor Ufd1 extract CENP-A from centromeric chromatin and can induce chromosome elimination in the fission yeast Schizosaccharomyces pombe. LID - 10.1242/bio.060287 [doi] LID - bio060287 AB - CENP-A determines the identity of the centromere. Because the position and size of the centromere and its number per chromosome must be maintained, the distribution of CENP-A is strictly regulated. In this study, we have aimed to understand mechanisms to regulate the distribution of CENP-A (Cnp1SP) in fission yeast. A mutant of the ufd1+ gene (ufd1-73) encoding a cofactor of Cdc48 ATPase is sensitive to Cnp1 expressed at a high level and allows mislocalization of Cnp1. The level of Cnp1 in centromeric chromatin is increased in the ufd1-73 mutant even when Cnp1 is expressed at a normal level. A preexisting mutant of the cdc48+ gene (cdc48-353) phenocopies the ufd1-73 mutant. We have also shown that Cdc48 and Ufd1 proteins interact physically with centromeric chromatin. Finally, Cdc48 ATPase with Ufd1 artificially recruited to the centromere of a mini-chromosome (Ch16) induce a loss of Cnp1 from Ch16, leading to an increased rate of chromosome loss. It appears that Cdc48 ATPase, together with its cofactor Ufd1 remove excess Cnp1 from chromatin, likely in a direct manner. This mechanism may play a role in centromere disassembly, a process to eliminate Cnp1 to inactivate the kinetochore function during development, differentiation, and stress response. CI - (c) 2024. Published by The Company of Biologists Ltd. FAU - Nakase, Yukiko AU - Nakase Y AUID- ORCID: 0000-0002-2669-5539 AD - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 606-8501, Japan. FAU - Murakami, Hiroaki AU - Murakami H AUID- ORCID: 0000-0003-0283-7106 AD - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 606-8501, Japan. FAU - Suma, Michiko AU - Suma M AUID- ORCID: 0009-0009-7414-7557 AD - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 606-8501, Japan. FAU - Nagano, Kaho AU - Nagano K AD - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 606-8501, Japan. FAU - Wakuda, Airi AU - Wakuda A AD - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 606-8501, Japan. FAU - Kitagawa, Teppei AU - Kitagawa T AD - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 606-8501, Japan. FAU - Matsumoto, Tomohiro AU - Matsumoto T AUID- ORCID: 0000-0001-6199-5126 AD - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 606-8501, Japan. LA - eng GR - 20K06485/Japan Society for the Promotion of Science/ GR - Kyoto University/ PT - Journal Article DEP - 20240408 PL - England TA - Biol Open JT - Biology open JID - 101578018 RN - 0 (Chromatin) RN - 0 (Centromere Protein A) RN - 0 (Histones) RN - 0 (Schizosaccharomyces pombe Proteins) RN - 0 (Chromosomal Proteins, Non-Histone) RN - EC 3.6.1.- (Adenosine Triphosphatases) RN - 0 (Plant Extracts) RN - 0 (Cnp1 protein, S pombe) SB - IM MH - Chromatin/genetics/metabolism MH - *Schizosaccharomyces/genetics/metabolism MH - Centromere Protein A/genetics/metabolism MH - Histones/metabolism MH - *Schizosaccharomyces pombe Proteins/genetics/metabolism MH - Chromosomal Proteins, Non-Histone/genetics/metabolism MH - Centromere/genetics/metabolism MH - Adenosine Triphosphatases/metabolism MH - Plant Extracts/metabolism PMC - PMC11033524 OTO - NOTNLM OT - Cdc48 OT - Centromere OT - Chromosome OT - Cnp1 OT - Pombe OT - Ufd1 COIS- Competing interests The authors declare no competing or financial interests. EDAT- 2024/03/25 12:43 MHDA- 2024/04/09 06:45 PMCR- 2024/04/08 CRDT- 2024/03/25 09:34 PHST- 2023/12/19 00:00 [received] PHST- 2024/03/14 00:00 [accepted] PHST- 2024/04/09 06:45 [medline] PHST- 2024/03/25 12:43 [pubmed] PHST- 2024/03/25 09:34 [entrez] PHST- 2024/04/08 00:00 [pmc-release] AID - 345663 [pii] AID - BIO060287 [pii] AID - 10.1242/bio.060287 [doi] PST - ppublish SO - Biol Open. 2024 Apr 15;13(4):bio060287. doi: 10.1242/bio.060287. Epub 2024 Apr 8.