Publications by authors named "Takenori Toda"
Faithful transfer of parental histones to newly replicated daughter DNA strands is critical for inheritance of epigenetic states. Although replication proteins that facilitate parental histone transfer have been identified, how intact histone H3-H4 tetramers travel from the front to the back of the replication fork remains unknown. Here, we use AlphaFold-Multimer structural predictions combined with biochemical and genetic approaches to identify the Mrc1/CLASPIN subunit of the replisome as a histone chaperone.
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- - In fission yeast, the protein Mrc1 is essential for transferring parental histones H3 and H4 to the lagging strand of newly synthesized DNA, ensuring the proper inheritance of epigenetic traits.
- - Mrc1 helps Mcm2 and DNA polymerase alpha, two important proteins that bind histones, to interact and optimize the parental histone transfer process.
- - Interestingly, Mrc1's role in histone transfer and epigenetic memory is separate from its traditional functions in DNA replication and checkpoint activation, indicating a complex mechanism underlying epigenetic inheritance.
Inheritance of epigenetic information is critical for maintaining cell identity. The transfer of parental histone H3-H4 tetramers, the primary carrier of epigenetic modifications on histone proteins, represents a crucial yet poorly understood step in the inheritance of epigenetic information. Here, we show the lagging strand DNA polymerase, Pol δ, interacts directly with H3-H4 and that the interaction between Pol δ and the sliding clamp PCNA regulates parental histone transfer to lagging strands, most likely independent of their roles in DNA synthesis.
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- Chromatin-based epigenetic memory depends on how parental histone H3-H4 tetramers are distributed in new DNA strands, with Mcm2 and Dpb3/4 playing key roles in this process.
- A study using fission yeast revealed that a mutation in Mcm2 significantly hinders heterochromatin inheritance, while mutations in Dpb3/4 only slightly affect it; interestingly, mutations in both can stabilize inheritance.
- The FACT histone chaperone is crucial for transferring parental histones to both strands, working with Mcm2 and Dpb3/4 to ensure proper density and distribution during DNA replication, which is essential for maintaining epigenetic inheritance.
Article Synopsis
- Pediatric high-grade gliomas (pHGG) are really tough brain tumors that usually can't be cured and often have mutations in a gene called histone H3.3.
- These mutations cause problems with how genes work and can make the brain cells unstable.
- Researchers found that a DNA repair enzyme called PNKP helps the cancer cells survive, which could be a new way to create treatments specifically for these mutated cells.
The epigenetic landscape of a cell frequently changes in response to fluctuations in nutrient levels, but the mechanistic link is not well understood. In fission yeast, the JmjC domain protein Epe1 is critical for maintaining the heterochromatin landscape. While loss of Epe1 results in heterochromatin expansion, overexpression of Epe1 leads to defective heterochromatin.
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