Genome complexity: protecting DNA integrity (Introduction)

by David Turell , Wednesday, October 03, 2018, 19:21 (2031 days ago) @ David Turell

Another system is described. Finding a multiplicity of protections is not surprising, since DNA replication must be exact:

https://www.sciencedaily.com/releases/2018/10/181003090314.htm

"Researchers from Tokyo Metropolitan University and the FIRC Institute of Molecular Oncology (IFOM) in Italy have succeeded in depleting AND-1, a key protein for DNA replication, by using a recently developed conditional protein degradation system. Consequently, they were able to gain unprecedented access to the mechanism behind how AND-1 works during DNA replication and cell proliferation in vertebrate cells, demonstrating that AND-1 has two different functions during DNA replication mediated by different domains of AND-1.

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"The AND-1/Ctf4 protein is a key player in DNA replication, and is found in a vast range of living organisms, from fungi to vertebrates. Ctf4/AND-1 is essential in some organisms, but whether it is an essential gene for cell proliferation in vertebrates has not been shown experimentally. Moreover, how loss of AND-1 affects cell proliferation is not known.

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"When done correctly, DNA replication should result in the formation of new double-stranded DNA helices. Authors used transmission electron microscopy (TEM) to visualize DNA replication intermediates and observed newly synthesized DNA having abnormally long single stranded DNA at the fork branching point in the absence of AND-1. They hypothesized that this was due to a DNA cleaving enzyme, a nuclease, disrupting the process of strands being disassembled. On further addition of a compound that suppresses the action of a particular nuclease, MRE11, they were able to successfully revert the abnormal replication fork phenotype and recover cell division, explicitly demonstrating the key role played by AND-1 in preventing nascent DNA cleavage by the nuclease during replication. Further analysis revealed that a specific part of the protein called WD40 repeats was responsible for preventing the accumulation of damage to the strand."

Comment: An expected finding. By design.