RT Journal Article
SR Electronic
T1 Mitotic replisome disassembly in vertebrates
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 418368
DO 10.1101/418368
A1 Sara Priego Moreno
A1 Rebecca M. Jones
A1 Divyasree Poovathumkadavil
A1 Agnieszka Gambus
YR 2018
UL http://biorxiv.org/content/early/2018/09/15/418368.abstract
AB Recent years have brought a breakthrough in our understanding of the process of eukaryotic DNA replication termination. We have shown that the process of replication machinery (replisome) disassembly at the termination of DNA replication forks in S-phase of the cell cycle is driven through polyubiquitylation of one of the replicative helicase subunits Mcm7. Our previous work in C.elegans embryos suggested also an existence of a back-up pathway of replisome disassembly in mitosis. Here we show, that in Xenopus laevis egg extract, any replisome retained on chromatin after S-phase is indeed removed from chromatin in mitosis. This mitotic disassembly pathway depends on formation of K6 and K63 ubiquitin chains on Mcm7 by TRAIP ubiquitin ligase and activity of p97/VCP protein segregase. The mitotic replisome pathway is therefore conserved through evolution in higher eukaryotes. However, unlike in lower eukaryotes it does not require SUMO modifications. This process can also remove any helicases from chromatin, including “active” stalled ones, indicating a much wider application of this pathway than just a “back-up” for terminated helicases.