Phosphorylation of H2A by Bub1 Prevents Chromosomal Instability Through Localizing Shugoshin

Kawashima, Shinichi; Yamagishi, Yuya; Honda, Takashi; Ishiguro, Kei‐ichiro; Watanabe, Yoshinori

doi:10.1126/science.1180189

Cited by 455 publications

(628 citation statements)

References 40 publications

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“…In mammalian cells, the Williams Syndrome Transcription Factor-SNF2H (Sucrose NonFermentable 2H) chromatin remodeling complex plays a vital role in the DNA damage response and phosphorylates tyrosine 142 of H2A.X (Xiao et al, 2009). In addition to DNA damage, phosphorylation of H2A at serine 121 by Bub1 (Budding Uninhibited By Benzimidazoles 1) regulates the localization of shugoshin to prevent chromosomal instability (Kawashima et al, 2010), and phosphorylation of histone H2A at tyrosine 56 by Casein Kinase II (CK2) regulates transcriptional elongation (Basnet et al, 2014). In maize (Zea mays), the phosphorylation of H2A at threonine 133 is associated with centromere function and maintenance during meiosis (Dong and Han, 2012).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of Histone H2A at Serine 95: A Plant-Specific Mark Involved in Flowering Time Regulation and H2A.Z Deposition

Wang

Zhang

et al. 2017

Plant Cell

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Phosphorylation of histone H3 affects transcription, chromatin condensation, and chromosome segregation. However, the role of phosphorylation of histone H2A remains unclear. Here, we found that Arabidopsis thaliana MUT9P-LIKE-KINASE (MLK4) phosphorylates histone H2A on serine 95, a plant-specific modification in the histone core domain. Mutations in MLK4 caused late flowering under long-day conditions but no notable phenotype under short days. MLK4 interacts with CIRCADIAN CLOCK ASSOCIATED1 (CCA1), which allows MLK4 to bind to the GIGANTEA (GI) promoter. CCA1 interacts with YAF9a, a co-subunit of the Swi2/Snf2-related ATPase (SWR1) and NuA4 complexes, which are responsible for incorporating the histone variant H2A.Z into chromatin and histone H4 acetylase activity, respectively. Importantly, loss of MLK4 function led to delayed flowering by decreasing phosphorylation of H2A serine 95, along with attenuated accumulation of H2A.Z and the acetylation of H4 at GI, thus reducing GI expression. Together, our results provide insight into how phosphorylation of H2A serine 95 promotes flowering time and suggest that phosphorylation of H2A serine 95 modulated by MLK4 is required for the regulation of flowering time and is involved in deposition of the histone variant H2A.Z and H4 acetylation in Arabidopsis.

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Section: Introductionmentioning

confidence: 99%

Phosphorylation of Histone H2A at Serine 95: A Plant-Specific Mark Involved in Flowering Time Regulation and H2A.Z Deposition

Wang

Zhang

et al. 2017

Plant Cell

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“…Bub1 in particular, has multiple roles, as it monitors kinetochoremicrotubule attachments, contributes to the unification of sister chromatids, and prevents the removal of the cohesin Rec8 from centromeric regions (Bernard et al 2001). At the molecular level, Bub1 regulates this latter function by controlling the centromeric localization of Sgo1 through the phosphorylation of Histone H2A (Kawashima et al 2010). The recruitment of Sgo1 in turn protects Rec8 from degradation during meiosis by safeguarding it from the separase (Kitajima et al 2004).…”

Section: The Meiotic Spindle Assembly Checkpointmentioning

confidence: 99%

The Spindle Assembly Checkpoint: Clock or Domino?

Medina-Redondo

Meraldi

2011

Results and Problems in Cell Differentiation

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In each cell division, the newly duplicated chromosomes must be evenly distributed between the sister cells. Errors in this process during meiosis or mitosis are equally fatal: improper segregation of the chromosome 21 during human meiosis leads to Down syndrome (Conley, Aneuploidy: etiology and mechanisms, pp 1985), whereas in somatic cells, aneuploidy has been linked to carcinogenesis, by unbalancing the ratio of oncogenes and tumor suppressors (Holland and Cleveland, Nat Rev Mol Cell Biol 10(7): 478-487, 2009; Yuen et al., Curr Opin Cell Biol 17(6):576-582, 2005). Eukaryotic cells have developed a mechanism, known as the spindle assembly checkpoint, to detect erroneous attachment of chromosomes to the mitotic/meiotic spindle and delay the cell cycle to give enough time to resolve these defects. Research in the last 20 years, has demonstrated that the spindle assembly checkpoint is not only a pure checkpoint pathway, but plays a constitutive role in every cell cycle. Here, we review our current knowledge of how the spindle assembly checkpoint is integrated into the cell cycle machinery, and discuss some of the questions that have to be addressed in the future.

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“…In addition to the SAC, Bub1 also functions in recruiting the cohesin protector Sgo1 to the centromeric region. 6 However, the synergistic effects of nup132D and bub1D in sister chromatid segregation do not simply occur because of the loss of Sgo1, given that simultaneous deletion of mad2 and sgo1 in the nup132D mutant does not phenocopy the nup132Dbub1D mutant. 1 This result suggests that Bub1 has another regulatory role in meiotic kinetochore assembly.…”

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confidence: 99%