Biochemical controls: cell division DNA replication (Introduction)

by David Turell @, Wednesday, May 31, 2023, 17:43 (379 days ago) @ David Turell

A major cell machine described:

"Researchers have revealed, at high-resolution, the structure of a human protein complex named SIN3B, which is a 'nanomachine' involved in regulating cell division. Cell division is a fundamental process for life which, if it becomes uncontrolled, can lead to cancer.

"The team also discovered several interaction sites within these proteins, which can be mutated in people with cancer.

"This is the first time the high-resolution structure of a human protein complex of this kind has been determined.


"The DNA is packaged up inside each cell in a structure known as chromatin, where it is wrapped around proteins called histones forming nucleosomes, which are like beads on a string.


"The histones have linear structures coming off them—these histone tails can undergo a process known as lysine acetylation, performed by histone acetyl transferase enzymes (HATs), which helps ensure the chromatin is ready for DNA replication, DNA repair and gene transcription. Other enzymes called histone deacetylases (HDACs) counteract the role of HATs—making the chromatin more compact thereby shutting down gene transcription.


" collaboration with Professor Jyoti Choudhary's group, at the ICR were able to determine the structure of SIN3B, which surrounds the HDAC enzyme—activating it and allowing it to recognize and deacetylate nucleosomes.

"The findings, published in the journal Nature Communications, show that SIN3B helps to recruit other proteins, called PHF12 and MORF4L1, which allow the nanomachine to bind to the histone tail so it can inhibit transcription.

"Beyond discovering how the nanomachine assembles and does its job in regulating cell division, the researchers also showed where mutations in the proteins can occur in cancer patients—these faults stop healthy processes that suppress uncontrolled cell division and cancer.


"'We've known about HDAC enzymes for 50 years, but we didn't know how they specifically target the histones involved in wrapping up the DNA in our cells into a compact package in the nucleus. It's hugely exciting to be able to see something for the first time that no one else has ever seen before.'"

Comment: the article has a picture of the giant structure. There are so many steps in cell reproduction, the mechanisms are irreducibly complex and must have been designed all at once. A giant enzyme is designed with exact amino acids in exact positions for proper function.

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