A team of researchers from the Department of Biological Sciences at UNIST has achieved a significant breakthrough in understanding how brain proteins can help alleviate complications arising from DNA replication stress. This discovery holds immense potential for advancing treatments for various diseases, including cancer, neurological disorders, and age-related conditions that result from disruptions in DNA replication.
The combined RPA molecules then undergo phosphorylation—ainvolving attachment of phosphate groups composed of phosphorus and oxygen. Phosphorylated RPA recruits other proteins that help alleviate replication stress at specific sites along the DNA strand—restoring normal activity.
Interestingly, RPA exhibits weak or strong binding affinity towards single-stranded regions during its interaction with DNA. Through their investigation involving NSMF proteins, the research team discovered that NSMF selectively displaces some weakly bound RPAs while promoting a transition into more stable binding modes for the remaining RPAs.
This shift favors an enhanced phosphorylation process, catalyzed by the ataxia telangiectasia and RAD3-related kinase—an enzyme crucial for DNA damage response. The team's findings demonstrate that this mechanism accelerates the relief of replication stress. "This study has significant potential to impact treatments related to cancer, neurological disorders, and age-related conditions by unraveling molecular mechanisms associated with DNA"Considering NSMF's close relationship with Kallmann syndrome, we anticipate its contribution to advancements in treating this disease," added Yujin Kang, the first author of the study.
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