Journal
CELL CYCLE
Volume 14, Issue 7, Pages 1001-1009Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2015.1007001
Keywords
CDK; DDK; cell cycle; checkpoint; Ctf4/And-1; DNA replication; Mcm10; RecQL4
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Funding
- National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0015907, 2009-0072305]
- National Research Foundation of Korea [2011-0015907, 2009-0072305] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Though RecQL4 was shown to be essential for the initiation of DNA replication in mammalian cells, its role in initiation is poorly understood. Here, we show that RecQL4 is required for the origin binding of Mcm10 and Ctf4, and their physical interactions and association with replication origins are controlled by the concerted action of both CDK and DDK activities. Although RecQL4-dependent binding of Mcm10 and Ctf4 to chromatin can occur in the absence of pre-replicative complex, their association with replication origins requires the presence of the pre-replicative complex and CDK and DDK activities. Their association with replication origins and physical interactions are also targets of the DNA damage checkpoint pathways which prevent initiation of DNA replication at replication origins. Taken together, the RecQL4-dependent association of Mcm10 and Ctf4 with replication origins appears to be the first important step controlled by S phase promoting kinases and checkpoint pathways for the initiation of DNA replication in human cells.
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