PT  - JOURNAL ARTICLE
AU  - Sara Priego Moreno
AU  - Rebecca M Jones
AU  - Divyasree Poovathumkadavil
AU  - Shaun Scaramuzza
AU  - Agnieszka Gambus
TI  - Mitotic replisome disassembly depends on TRAIP ubiquitin ligase activity
AID  - 10.26508/lsa.201900390
DP  - 2019 Apr 01
TA  - Life Science Alliance
PG  - e201900390
VI  - 2
IP  - 2
4099  - https://www.life-science-alliance.org/content/2/2/e201900390.short
4100  - https://www.life-science-alliance.org/content/2/2/e201900390.full
SO  - Life Sci. Alliance2019 Apr 01; 2
AB  - We have shown previously that the process of replication machinery (replisome) disassembly at the termination of DNA replication forks in the S-phase is driven through polyubiquitylation of one of the replicative helicase subunits (Mcm7) by Cul2LRR1 ubiquitin ligase. Interestingly, upon inhibition of this pathway in Caenorhabditis elegans embryos, the replisomes retained on chromatin were unloaded in the subsequent mitosis. Here, we show that this mitotic replisome disassembly pathway exists in Xenopus laevis egg extract and we determine the first elements of its regulation. The mitotic disassembly pathway depends on the formation of K6- and K63-linked ubiquitin chains on Mcm7 by TRAIP ubiquitin ligase and the activity of p97/VCP protein segregase. Unlike in lower eukaryotes, however, it does not require SUMO modifications. Importantly, we also show that this process can remove all replisomes from mitotic chromatin, including stalled ones, which indicates a wide application for this pathway over being just a “backup” for terminated replisomes. Finally, we characterise the composition of the replisome retained on chromatin until mitosis.