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The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.

ABSTRACT: Phosphofurin acidic cluster sorting protein-1 (PACS-1) is a multifunctional membrane traffic regulator that plays important roles in organ homeostasis and disease. In this study, we elucidate a novel nuclear function for PACS-1 in maintaining chromosomal integrity. PACS-1 progressively accumulates in the nucleus during cell cycle progression, where it interacts with class I histone deacetylases 2 and 3 (HDAC2 and HDAC3) to regulate chromatin dynamics by maintaining the acetylation status of histones. PACS-1 knockdown results in the proteasome-mediated degradation of HDAC2 and HDAC3, compromised chromatin maturation, as indicated by elevated levels of histones H3K9 and H4K16 acetylation, and, consequently, increased replication stress-induced DNA damage and genomic instability.

SUBMITTER: Mani C

PROVIDER: S-EPMC7085454 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.

Mani Chinnadurai C Tripathi Kaushlendra K Luan Shan S Clark David W DW Andrews Joel F JF Vindigni Alessandro A Thomas Gary G Palle Komaraiah K

Oncogene 20200127 12

Phosphofurin acidic cluster sorting protein-1 (PACS-1) is a multifunctional membrane traffic regulator that plays important roles in organ homeostasis and disease. In this study, we elucidate a novel nuclear function for PACS-1 in maintaining chromosomal integrity. PACS-1 progressively accumulates in the nucleus during cell cycle progression, where it interacts with class I histone deacetylases 2 and 3 (HDAC2 and HDAC3) to regulate chromatin dynamics by maintaining the acetylation status of hist ...[more]

PMID: 31988453

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