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Comment
. 2012 Sep 12;31(18):3650-2.
doi: 10.1038/emboj.2012.238. Epub 2012 Aug 14.

Rif1 choreographs DNA replication timing

Mirit I Aladjem  1
Affiliations
Comment

Rif1 choreographs DNA replication timing

Mirit I Aladjem. EMBO J. .

Abstract

EMBO J (2012) 31 18, 3678–3690 doi:; DOI: 10.1038/emboj.2012.214; published online July 31 2012

EMBO J (2012) 31 18, 3667–3677; doi:; DOI: 10.1038/emboj.2012.180; published online July 31 2012

Eukaryotic cells duplicate their genome in a pre-determined order that appears to reflect a fundamental property of chromatin. Each chromosomal region replicates at a consistent, developmental- and tissue-specific time during the S phase of the cell cycle, and regions that replicate at the same time form distinct patterns in three-dimensional nuclear space. Although orderly progression of DNA replication is important for insuring stable genetic and epigenetic inheritance, the mechanisms underlying replication patterns have yet to be elucidated. Two reports in The EMBO Journal now identify a protein, Rif1, as a novel global determinant of the mammalian DNA replication program, and provide a link between higher order chromatin assembly and proper cell-cycle progression.

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Conflict of interest statement

The author declares that she has no conflict of interest.

Figures

Figure 1
Figure 1
Rif1 binds chromatin during the G1 phase of the cell cycle. Rif1 binding occurs concomitant with the binding of the pre-replication complex (purple) and recruitment of replicative helicase components (blue), but the two binding events are independent of each other. In early replicating chromatin regions, Rif1 binding does not interfere with the activation of DNA replication by S phase-specific kinases acting on the replicative helicase component Cdc45. Replication therefore can occur early during S phase with the two DNA strands becoming separated by the activated helicase. By contrast, Rif1 bound to late-replicating chromatin domains prevents activation of DNA replication by S-phase kinases, possibly by interfering with the interaction of Cdc45 with chromatin. When Rif1 is absent, the replication timing program is disrupted. As proposed by Yamazaki et al (2012) (illustrated in Figure 6 of that publication), Rif1 might delay replication by facilitating the formation of tight nuclear matrix-attached loops in heterochromatin.
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Comment on

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