Share This Author
Chk1‐deficient tumour cells are viable but exhibit multiple checkpoint and survival defects
Chk1 is dispensable for normal cell division in somatic DT40 cells but is essential for DNA damage‐induced G2/M arrest and a subset of replication checkpoint responses, which promote tumour cell survival after perturbations of DNA structure or metabolism.
The yeast CDC9 gene encodes both a nuclear and a mitochondrial form of DNA ligase I
Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation.
Interestingly, clonogenic survival assays showed that transient inhibition of ATM is sufficient to sensitize cells to IR and suggests that therapeutic radiosensitization may only require ATM inhibition for short periods of time.
DNA mediated chromatin pull-down for the study of chromatin replication
- Anna E. Kliszczak, M. Rainey, B. Harhen, F. Boisvert, C. Santocanale
- BiologyScientific reports
- 19 September 2011
A simple experimental approach is described that allows chromatin to be captured and its content analysed after in vivo replication and labeling of DNA by cellular DNA polymerases and it is shown that this technique is highly specific and that proteins bound to the replicated DNA can be analyzed by both immunological techniques and large scale mass spectrometry.
Chk1-Dependent S-M Checkpoint Delay in Vertebrate Cells Is Linked to Maintenance of Viable Replication Structures
The results suggest that Chk1 maintains the S-M checkpoint indirectly by preserving the viability of replication structures and that it is the continued presence of such structures, rather than the activation of Chk 1 per se, which delays mitosis until DNA replication is complete.
Requirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpoint
Using small molecule kinase inhibitors, PLK1 and Aurora B cooperate to avoid mitotic slippage upon microtubule depolymerization and to promote their reciprocal recruitment at kinetochores.
ATR Restrains DNA Synthesis and Mitotic Catastrophe in Response to CDC7 Inhibition.
Chk2 is required for optimal mitotic delay in response to irradiation-induced DNA damage incurred in G2 phase
It is suggested that this function of Chk2 could contribute to tumour suppression, since cell division with low levels of spontaneous damage is likely to promote genetic instability and thus carcinogenesis.
The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase.
- E. McGarry, D. Gaboriau, M. Rainey, Umberto Restuccia, A. Bachi, C. Santocanale
- BiologyCancer research
- 15 April 2016
A novel role for USP9X is revealed in the maintenance of genomic stability during DNA replication and potential mechanistic insights into its tumor suppressor role in certain malignancies are provided.
DNA Replication Dynamics and Cellular Responses to ATP Competitive CDC7 Kinase Inhibitors.
- M. Rainey, Huong Quachthithu, D. Gaboriau, C. Santocanale
- Biology, ChemistryACS chemical biology
- 7 June 2017
It is shown that DNA replication and cell proliferation can occur with reduced CDC7 activity for at least 5 days and that the bulk of DNA synthesis is not tightly coupled to MCM2 phosphorylation, which provides guidance for the development of next generation CDC7 inhibitors.