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Commun Biol 2023 Jul 29;61:788. doi: 10.1038/s42003-023-05172-8.
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Rif1 restrains the rate of replication origin firing in Xenopus laevis.

Haccard O , Ciardo D , Narrissamprakash H , Bronchain O , Kumagai A , Dunphy WG , Goldar A , Marheineke K .

Metazoan genomes are duplicated by the coordinated activation of clusters of replication origins at different times during S phase, but the underlying mechanisms of this temporal program remain unclear during early development. Rif1, a key replication timing factor, inhibits origin firing by recruiting protein phosphatase 1 (PP1) to chromatin counteracting S phase kinases. We have previously described that Rif1 depletion accelerates early Xenopus laevis embryonic cell cycles. Here, we find that in the absence of Rif1, patterns of replication foci change along with the acceleration of replication cluster activation. However, initiations increase only moderately inside active clusters. Our numerical simulations suggest that the absence of Rif1 compresses the temporal program towards more homogeneity and increases the availability of limiting initiation factors. We experimentally demonstrate that Rif1 depletion increases the chromatin-binding of the S phase kinase Cdc7/Drf1, the firing factors Treslin, MTBP, Cdc45, RecQL4, and the phosphorylation of both Treslin and MTBP. We show that Rif1 globally, but not locally, restrains the replication program in early embryos, possibly by inhibiting or excluding replication factors from chromatin.

PubMed ID: 37516798
PMC ID: PMC10387115
Article link: Commun Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cdc45 mtbp npy4r orc2 recql4 rif1 ticrr
GO keywords: cell cycle [+]
Antibodies: Tuba4a Ab3 cdc45 Ab4 cdc7 Ab1 mcm7 Ab3 mtbp Ab1 orc1 Ab3 orc2 Ab2 recql4 Ab1 rif1 Ab1 ticrr Ab1 topbp1 Ab1

Article Images: [+] show captions
References [+] :
Alver, Reversal of DDK-Mediated MCM Phosphorylation by Rif1-PP1 Regulates Replication Initiation and Replisome Stability Independently of ATR/Chk1. 2017, Pubmed, Xenbase