Publication Date:
2013-05-25
Description:
Treslin/TICRR (TopBP1-interacting, replication stimulating protein/TopBP1-interacting, checkpoint, and replication regulator), the human ortholog of the yeast Sld3 protein, is an essential DNA replication factor that is regulated by cyclin-dependent kinases and the DNA damage checkpoint. We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle. We show that MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holohelicase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, we found MTBP is required for DNA replication irrespective of a cell's p53 status. We propose that MTBP acts with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boos, Dominik -- Yekezare, Mona -- Diffley, John F X -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2013 May 24;340(6135):981-4. doi: 10.1126/science.1237448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK London Research Institute (LRI), Clare Hall Laboratories, South Mimms, Herts., UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704573" target="_blank"〉PubMed〈/a〉
Keywords:
Carrier Proteins/genetics/*metabolism
;
Cell Cycle Proteins/*metabolism
;
Chromatin/metabolism
;
DNA Damage
;
DNA Replication/genetics/*physiology
;
DNA-Binding Proteins/metabolism
;
G1 Phase Cell Cycle Checkpoints
;
HeLa Cells
;
Humans
;
Proliferating Cell Nuclear Antigen/metabolism
;
RNA Interference
;
RNA, Small Interfering/genetics
;
*Replication Origin
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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