Abstract
Rpb9 is a non-essential subunit of RNA polymerase II that is involved in DNA transcription and repair. In budding yeast, deletion of RPB9 causes several phenotypes such as slow growth and temperature sensitivity. We found that simultaneous mutation of multiple N-terminal lysines within histone H3 was lethal in rpb9Δ cells. Our results indicate that hypoacetylation of H3 leads to inefficient repair of DNA double-strand breaks, while activation of the DNA damage checkpoint regulators γH2A and Rad53 is suppressed in Rpb9-deficient cells. Combination of H3 hypoacetylation with the loss of Rpb9 leads to genomic instability, aberrant segregation of chromosomes in mitosis, and eventually to cell death. These results indicate that H3 acetylation becomes essential for efficient DNA repair and cell survival if a DNA damage checkpoint is defective.
Highlights
To protect genomic integrity, cells must continuously detect and repair DNA damage
Ubiquitylation of H2B has been implicated both in regulation of RNA polymerase II (RNAPII)-dependent transcription and in DNA damage response. It is needed for proper activation of the DNA damage checkpoint, timely initiation of DSB repair, and for recruitment of structure-specific endonucleases to the sites of DNA repair[26,27,28]. These genetic interactions suggest that chromatin modifications and careful regulation of the DNA damage response become essential for cell viability in the absence of Rpb[9]
We hypothesized that rpb9Δ cells might be sensitive to H3 modifications that are crucial for chromatin regulation and genome maintenance
Summary
Cells must continuously detect and repair DNA damage. Among different types of DNA lesions, double-strand DNA breaks (DSBs) are the most harmful, as they can lead to translocations and deletions of large fragments of chromosomes. Ubiquitylation of H2B has been implicated both in regulation of RNAPII-dependent transcription and in DNA damage response It is needed for proper activation of the DNA damage checkpoint, timely initiation of DSB repair, and for recruitment of structure-specific endonucleases to the sites of DNA repair[26,27,28]. These genetic interactions suggest that chromatin modifications and careful regulation of the DNA damage response become essential for cell viability in the absence of Rpb[9]. When H3 hypoacetylation is combined with depletion of Rpb[9], defective DNA damage response and unrepaired DNA lesions lead to genomic instability, aberrant segregation of DNA in mitosis and eventually cell death
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
