Once in the Replicating state, hepatocytes maintain replication until natural requiescence or buildup of extracellular matrix (ECM) induces them back to the Quiescent state.
Using a newly created wrn DT40 that lacks any detectable transcript, we show that WRN operates in a pathway dependent on REV1 to maintain replication fork progression following DNA damage and that RAD18-dependent post-replicative gap filling provides an important backup activity when WRN is lost.
The fork-shift model, which does not require origin relocation, is influenced by cis-elements and trans-factors associated with driving and maintaining replication forks.
We were interested in finding cis-elements that function as chromatin domain boundaries involved in maintaining replication timing domains.
EBNA-1 is a DNA binding protein that maintains replication of the EBV genome within infected cells.
But the targets for downregulated miR-148a within ORF1a, M, S and E might escape repression and maintain replication at a lower rate.
These studies establish that Tim-Tipin-Claspin function together as components of the mammalian and yeast replisome that are required for maintaining replication fork stability at programmed pause sites and during conditions of DNA damage.
Yeast orthologues of Tim and Tipin maintain replication fork stability at fork barriers, but the precise mechanism of these proteins and the function of the fork barriers remain enigmatic.
The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites.
RAD51 maintains replication fork integrity by binding to RPA-coated ssDNA; therefore, it is likely DMC1 also maintains replication fork integrity in GBM cells.
The ATR protein kinase senses problems during DNA replication and, in the event of stalled DNA replication, maintains replication fork stability and prevents cell cycle progression.
