Genome complexity: DNA repair at molecular level (Introduction)

by David Turell , Friday, March 18, 2022, 15:03 (770 days ago) @ David Turell

Mind blowing complexity:

https://www.sciencemagazinedigital.org/sciencemagazine/18_march_2022/MobilePagedArticle...

Abstract:
"The tail of replication-dependent histone H3.1 varies from that of replication-independent H3.3 at the amino acid located at position 31 in plants and animals, but no function has been assigned to this residue to demonstrate a unique and conserved role for H3.1 during replication. We found that TONSOKU (TSK/TONSL), which rescues broken replication forks, specifically interacts with H3.1 via recognition of alanine 31 by its tetratricopeptide repeat domain. Our results indicate that genomic instability in the absence of ATXR5/ATXR6-catalyzed histone H3 lysine 27 monomethylation in plants depends on H3.1, TSK, and DNA polymerase theta (Pol θ). This work reveals an H3.1-specific function during replication and a common strategy used in multicellular eukaryotes for regulating post-replicative chromatin maturation and TSK, which relies on histone monomethyltransferases and reading of the H3.1 variant".

Conclusion:
"Overall, this work uncovers a role for the TPR domain of TSK in selectively interacting with the H3.1 variant. Previous work in human cell lines has shown that the TSK ortholog TONSL copurifies with H3.1 in affinity purification/biochemical fractionation assays (Display footnote number:28), and that TONSL-mediateddoublestranded DNA break repair depends on the H3.1 chaperone CAF-1 (Display footnote number:2). These findings, combined with our identification of the TPR domain of TSK/TONSL acting as an H3.1 reader, point to a model where post-replicative chro-matin maturation in plants and animals relies on similar mechanisms involving H3.1 and clade-specific enzymes that monomethylate histones to prevent TSK/TONSL binding (Fig. 4G). In plants, monomethylation occurs at H3.1 Lys27 via ATXR5/6 and prevents binding of TSK through the TPR domain. In animals, SET8-mediated monomethylation at H4 Lys20 interferes with TONSL binding via the ARD domain (Display footnote number:9). However, in both plants and animals, recruitment of TSK/TONSL to chromatin likely relies on the ability of the conserved TPR domain to preferentially interact with the H3.1 variant. Thus, our work reveals the importance of selectively incorporating H3.1 variants during DNA replication, as it confers a window of opportunity during the cell cycle for the TSK/TONSL DNA repair pathway to resolve broken replication forks."

Comment: This is obviously difficult to follow for those of us not working in this field. This mechanism is used by both plant and animal organisms with sexual reproduction in which DNA is wrapped around histone core molecules and is specifically designed to repair mistakes in which DNA is broken. This mechanism had to be present when sexual reproduction first appeared in evolution, or these forms of life would not have survived. Only comprehensive design can produce this.