NCBI Summary:
This gene product is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair. This protein possesses 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. It forms a checkpoint protein complex with RAD1 and HUS1. This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
General function
Cell cycle regulation
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Cellular localization
Nuclear
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Ovarian function
Early embryo development
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Rad9a is involved in chromatin decondensation and post-zygotic embryo development in mice. Huang L et al. (2018) Zygotic chromatin undergoes extensive reprogramming immediately after fertilization. It is generally accepted that maternal factors control this process. However, little is known about the underlying mechanisms. Here we report that maternal RAD9A, a key protein in DNA damage response pathway, is involved in post-zygotic embryo development, via a mouse model with conditional depletion of Rad9a alleles in oocytes of primordial follicles. Post-zygotic losses originate from delayed zygotic chromatin decondensation after depletion of maternal RAD9A. Pronucleus formation and DNA replication of most mutant zygotes are therefore deferred, which subsequently trigger the G2/M checkpoint and arrest development of most mutant zygotes. Delayed zygotic chromatin decondensation could also lead to increased reabsorption of post-implantation mutant embryos. In addition, our data indicate that delayed zygotic chromatin decondensation may be attributed to deferred epigenetic modification of histone in paternal chromatin after fertilization, as fertilization and resumption of secondary meiosis in mutant oocytes were both normal. More interestingly, most mutant oocytes could not support development beyond one-cell stage after parthenogenetic activation. Therefore, RAD9A may also play an important role in maternal chromatin reprogramming. In summary, our data reveal an important role of RAD9A in zygotic chromatin reprogramming and female fertility.//////////////////
Expression regulated by
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Ovarian localization
Oocyte
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Localization of the Drosophila rad9 protein to the nuclear membrane is regulated by the C-terminal region and is affected in the meiotic checkpoint. Kadir R et al. Rad9, Rad1, and Hus1 (9-1-1) are part of the DNA integrity checkpoint control system. It was shown previously that the C-terminal end of the human Rad9 protein, which contains a nuclear localization sequence (NLS) nearby, is critical for the nuclear transport of Rad1 and Hus1. In this study, we show that in Drosophila, Hus1 is found in the cytoplasm, Rad1 is found throughout the entire cell and that Rad9 (DmRad9) is a nuclear protein. More specifically, DmRad9 exists in two alternatively spliced forms, DmRad9A and DmRad9B, where DmRad9B is localized at the cell nucleus, and DmRad9A is found on the nuclear membrane both in Drosophila tissues and also when expressed in mammalian cells. Whereas both alternatively spliced forms of DmRad9 contain a common NLS near the C terminus, the 32 C-terminal residues of DmRad9A, specific to this alternative splice form, are required for targeting the protein to the nuclear membrane. We further show that activation of a meiotic checkpoint by a DNA repair gene defect but not defects in the anchoring of meiotic chromosomes to the oocyte nuclear envelope upon ectopic expression of non-phosphorylatable Barrier to Autointegration Factor (BAF) dramatically affects DmRad9A localization. Thus, by studying the localization pattern of DmRad9, our study reveals that the DmRad9A C-terminal region targets the protein to the nuclear membrane, where it might play a role in response to the activation of the meiotic checkpoint.