Combined Interactions of Plant Homeodomain and Chromodomain Regulate NuA4 Activity at DNA Double-Strand Breaks.
نویسندگان
چکیده
DNA double-strand breaks (DSBs) represent one of the most threatening lesions to the integrity of genomes. In yeast Saccharomyces cerevisiae, NuA4, a histone acetylation complex, is recruited to DSBs, wherein it acetylates histones H2A and H4, presumably relaxing the chromatin and allowing access to repair proteins. Two subunits of NuA4, Yng2 and Eaf3, can interact in vitro with methylated H3K4 and H3K36 via their plant homeodomain (PHD) and chromodomain. However, the roles of the two domains and how they interact in a combinatorial fashion are still poorly characterized. In this study, we generated mutations in the PHD and chromodomain that disrupt their interaction with methylated H3K4 and H3K36. We demonstrate that the combined mutations in both the PHD and chromodomain impair the NuA4 recruitment, reduce H4K12 acetylation at the DSB site, and confer sensitivity to bleomycin that induces DSBs. In addition, the double mutant cells are defective in DSB repair as judged by Southern blot and exhibit prolonged activation of phospho-S129 of H2A. Cells harboring the H3K4R, H3K4R, K36R, or set1Δ set2Δ mutant that disrupts H3K4 and H3K36 methylation also show very similar phenotypes to the PHD and chromodomain double mutant. Our results suggest that multivalent interactions between the PHD, chromodomain, and methylated H3K4 and H3K36 act in a combinatorial manner to recruit NuA4 and regulate the NuA4 activity at the DSB site.
منابع مشابه
The Role of Long Non Coding RNAs in the Repair of DNA Double Strand Breaks
DNA double strand breaks (DSBs) are abrasions caused in both strands of the DNA duplex following exposure to both exogenous and endogenous conditions. Such abrasions have deleterious effect in cells leading to genome rearrangements and cell death. A number of repair systems including homologous recombination (HR) and non-homologous end-joining (NHEJ) have been evolved to minimize the fatal effe...
متن کاملModeling the distribution of deposited energy by alpha particles from Radon 223 decay and its effect on DNA
The ionizing radiations, through physical and chemical processes, lead to simple and complex single- and double- strand breaks, as well as base lesions to the DNA. In this study, taking into account all the physical and chemical processes involved in the interaction of ionizing radiation with matter, the initial damage induced to DNA was evaluated for 5.7 MeV alpha-rays from Radon 223 isotope....
متن کاملResidual DNA double strand breaks correlates with excess acute toxicity from radiotherapy
Introduction: A high risk for development of severe side effects after radiotherapy may be correlated with high cellular radiosensitivity. To enhance radiation therapy efficiency a fast and reliable in-vitro test is desirable to identify radiosensitive patients. The aim of present study was to identify the mechanism of radiation induced DNA double-strand breaks (DSBs) and DSB r...
متن کاملThe study of dose gamma rays of 192Ir source on DNA single strand break (SSB) and DNA double strand break (DSB) in soft tissue phantom
Introduction: Passage of ionizing radiation through the organs of living creatures develops clusters of damaged nucleotides inside the DNA rounds. 192Ir Gamma source is one of the most widely used sources in brachytherapy of cervical and prostate cancer. Thus, in this research, we investigated the flux of photons and its resulting secondary electrons, the single-strand break (S...
متن کاملSimulation of strand breaks induced in DNA molecule by radiation of proton and Secondary particles using Geant4 code
Radiotherapy using various beams is one of the methods for treating cancer, Hadrons used to treat cancers that are near critical organs. The most important part of the cell that is damage by ionizing radiation is DNA. In this study, damages induced in the genetic material of living cells (DNA) defined by the atomic model from the protein data bank (PDB) have been studied by radiati...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Genetics
دوره 202 1 شماره
صفحات -
تاریخ انتشار 2016