TopBP1-mediated DNA processing during mitosis
| Autor: | Signe Korbo Christiansen, Vibe H. Oestergaard, Michael Lisby, Rune Troelsgaard Pedersen, Irene Gallina |
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| Rok vydání: | 2016 |
| Předmět: |
DNA Replication
0301 basic medicine Genome instability DNA re-replication DNA Repair DNA damage DNA repair Mitosis Eukaryotic DNA replication DNA-Directed DNA Polymerase Biology Immortal DNA strand hypothesis Cell Line 03 medical and health sciences Control of chromosome duplication Proliferating Cell Nuclear Antigen Animals Molecular Biology Genetics B-Lymphocytes Fanconi Anemia Complementation Group D2 Protein Extra View Ubiquitination DNA Cell Biology G2-M DNA damage checkpoint Nucleotidyltransferases 030104 developmental biology Carrier Proteins Chickens DNA Damage Developmental Biology |
| Zdroj: | Cell Cycle. 15:176-183 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2015.1128595 |
| Popis: | Maintenance of genome integrity is crucial to avoid cancer and other genetic diseases. Thus faced with DNA damage, cells mount a DNA damage response to avoid genome instability. The DNA damage response is partially inhibited during mitosis presumably to avoid erroneous processing of the segregating chromosomes. Yet our recent study shows that TopBP1-mediated DNA processing during mitosis is highly important to reduce transmission of DNA damage to daughter cells.1 Here we provide an overview of the DNA damage response and DNA repair during mitosis. One role of TopBP1 during mitosis is to stimulate unscheduled DNA synthesis at underreplicated regions. We speculated that such genomic regions are likely to hold stalled replication forks or post-replicative gaps, which become the substrate for DNA synthesis upon entry into mitosis. Thus, we addressed whether the translesion pathways for fork restart or post-replicative gap filling are required for unscheduled DNA synthesis in mitosis. Using genetics in the avian DT40 cell line, we provide evidence that unscheduled DNA synthesis in mitosis does not require the translesion synthesis scaffold factor Rev1 or PCNA ubiquitylation at K164, which serve to recruit translesion polymerases to stalled forks. In line with this finding, translesion polymerase η foci do not colocalize with TopBP1 or FANCD2 in mitosis. Taken together, we conclude that TopBP1 promotes unscheduled DNA synthesis in mitosis independently of the examined translesion polymerases. |
| Databáze: | OpenAIRE |
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