TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication

TY - JOUR

T1 - TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication

AU - Sonneville, Remi

AU - Bhowmick, Rahul

AU - Hoffmann, Saskia

AU - Mailand, Niels

AU - Hickson, Ian D

AU - Labib, Karim

PY - 2019/9

Y1 - 2019/9

N2 - The faithful segregation of eukaryotic chromosomes in mitosis requires that the genome be duplicated completely prior to anaphase. However, cells with large genomes sometimes fail to complete replication during interphase and instead enter mitosis with regions of incompletely replicated DNA. These regions are processed in early mitosis via a process known as mitotic DNA repair synthesis (MiDAS), but little is known about how cells switch from conventional DNA replication to MiDAS. Using the early embryo of the nematode Caenorhabditis elegans as a model system, we show that the TRAIP ubiquitin ligase drives replisome disassembly in response to incomplete DNA replication, thereby providing access to replication forks for other factors. Moreover, TRAIP is essential for MiDAS in human cells, and is important in both systems to prevent mitotic segregation errors. Our data indicate that TRAIP is a master regulator of the processing of incomplete DNA replication during mitosis in metazoa.

AB - The faithful segregation of eukaryotic chromosomes in mitosis requires that the genome be duplicated completely prior to anaphase. However, cells with large genomes sometimes fail to complete replication during interphase and instead enter mitosis with regions of incompletely replicated DNA. These regions are processed in early mitosis via a process known as mitotic DNA repair synthesis (MiDAS), but little is known about how cells switch from conventional DNA replication to MiDAS. Using the early embryo of the nematode Caenorhabditis elegans as a model system, we show that the TRAIP ubiquitin ligase drives replisome disassembly in response to incomplete DNA replication, thereby providing access to replication forks for other factors. Moreover, TRAIP is essential for MiDAS in human cells, and is important in both systems to prevent mitotic segregation errors. Our data indicate that TRAIP is a master regulator of the processing of incomplete DNA replication during mitosis in metazoa.

U2 - 10.7554/eLife.48686

DO - 10.7554/eLife.48686

M3 - Journal article

C2 - 31545170

SN - 2050-084X

VL - 8

JO - eLife

JF - eLife

M1 - e48686

ER -