One of the secrets of human DNA replication
In their recent Nature Communications paper Phosphate steering by flap endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability the Grasby group reports on their work on understanding human DNA replication.
A short summary written by Jane Grasby is included below
Working with international collaborators the Grasby lab have demonstrated how the human DNA hydrolysing enzyme flap endonuclease-1 (hFEN1) verifies its correct DNA substrate. During DNA replication and repair hFEN1 must prevent reactions of continuous DNAs to protect the genome. However, hFEN1 must allow reactions of discontinuous DNA structures such as those with single-stranded flaps. The work demonstrates that this specificity is achieved by threading the single-stranded DNA through a hole in protein. The threaded DNA flap is guided through the hole and positioned to react at a precise site using a process the group have termed “phosphate steering”.
Susan E. Tsutakawa, Mark J. Thompson, Andrew S. Arvai, Alexander J. Neil, Steven J. Shaw, Sana I. Algasaier, Jane C. Kim, L. David Finger, Emma Jardine, Victoria J. B. Gotham, Altaf S. Sarker, Mai Z. Her, Fahad Rashid, Samir M. Hamdan, Sergei M. Mirkin, Jane A. Grasby and John A. Tainer, Nature Communications 8, 15855 (2017) DOI: 10.1038/ncomms15855