title: HAT3-mediated acetylation of PCNA precedes PCNA monoubiquitination following exposure to UV radiation in Leishmania donovani.
abstract: Histone modifications impact various processes. In examining histone acetyltranferase HAT3 of Leishmania donovani, we find elimination of HAT3 causes decreased cell viability due to defects in histone deposition, and aberrant cell cycle progression pattern. HAT3 associates with proliferating cell nuclear antigen (PCNA), helping load PCNA onto chromatin in proliferating cells. HAT3-nulls show heightened sensitivity to UV radiation. Following UV exposure, PCNA cycles off/on chromatin only in cells expressing HAT3. Inhibition of the ubiquitin-proteasome pathway prior to UV exposure allows accumulation of chromatin-bound PCNA, and reveals that HAT3-nulls are deficient in PCNA monoubiquitination as well as polyubiquitination. While poor monoubiquitination of PCNA may adversely affect translesion DNA synthesis-based repair processes, polyubiquitination deficiencies may result in continued retention of chromatin-bound PCNA, leading to genomic instability. On suppressing the proteasome pathway we also find that HAT3 mediates PCNA acetylation in response to UV. HAT3-mediated PCNA acetylation may serve as a flag for PCNA ubiquitination, thus aiding DNA repair. While PCNA acetylation has previously been linked to its degradation following UV exposure, this is the first report linking a HAT-mediated PCNA acetylation to PCNA monoubiquitination. These findings add a new dimension to our knowledge of the mechanisms regulating PCNA ubiquitination post-UV exposure in eukaryotes.
authors.affiliation: Department of Microbiology, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021, India.
authors.forename: Devanand
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Microbiology, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021, India ss5gp@yahoo.co.in.
authors.forename: Swati
authors.initials: S
authors.lastname: Saha
mesh_terms: D000107:Acetylation; D002453:Cell Cycle; D002467:Cell Nucleus / Q000201:enzymology; D002843:Chromatin / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D007893:Leishmania donovani / Q000166:cytology / Q000201:enzymology* / Q000528:radiation effects; D008239:Lysine / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D014466:Ultraviolet Rays
chemical_list: D002843:Chromatin; D006657:Histones; D018809:Proliferating Cell Nuclear Antigen; D015800:Protozoan Proteins; D051548:Histone Acetyltransferases; D008239:Lysine