Kyoto, Japan -- Sometimes, the number needs to be just right. Meiotic cell division -- a fundamental process involved in sexual reproduction -- not only requires the proper protein to break chromosomes but also an appropriate number of DNA double-strand breaks that depend on this protein, called DSB-1.
Now, a team of researchers has discovered that the balance of DSB-1 phosphorylation possibly guarantees normal meiosis and genome stability, giving insight into the broad DSB machinery.
"The discovery of this phosphorylation pathway helps us gain a further understanding of the negative feedback control of DSBs," says the corresponding author Peter Carlton of Kyoto University.
To obtain successful meiosis, enzymes ATR kinase and PP4 phosphatase work in tandem to regulate DSB-1 phosphorylation, thereby maintaining a balance in DSB count.
ATR-dependent phosphorylation of DSB-1 down-regulates DSB formation, and PP4 in turn promotes DSB up-regulation.
During meiosis, chromosome pairs are connected by crossovers, or DNA exchanges. These form when chromosomes are repaired after being broken by programmed DSBs. While necessary to create crossovers on each chromosome, DNA breakage is also tightly controlled to protect the genome from excess damage.
"We think we have come closer to elucidating the mechanisms behind DSB regulation with the model organism C elegans, a nematode worm," Carlton reflects.
The aim of the study was to determine whether any phosphatase, such as PP4, acts to inhibit or regulate anti-DSB activity.
"Our combined approach of genetics, high-resolution imaging, and biochemistry supports this hypothesis, further demonstrating that DSBs strengthen chromosomal pairing and synapsis in C elegans."
【KURENAI ACCESS URL】
Heyun Guo, Ericca L Stamper, Aya Sato-Carlton, Masa A Shimazoe, Xuan Li, Liangyu Zhang, Lewis Stevens, KC Jacky Tam, Abby F Dernburg, Peter M Carlton (2022). Phosphoregulation of DSB-1 mediates control of meiotic double-strand break activity. eLife, 11:e77956.