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Sister chromatid cohesion establishment during DNA replication termination

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Abstract The cohesin complex tethers sister chromatids together from the moment they are generated in S-phase until their separation in anaphase 1,2 . This fundamental phenomenon, called sister chromatid cohesion, underpins orderly chromosome segregation. The replisome complex coordinates cohesion establishment with replication of parental DNA 3 . Cohesion can be established by cohesin complexes bound to DNA before replication 4,5 , but how replisome interaction with pre-loaded cohesin complexes results in cohesion is not known. Prevailing models suggest cohesion is established by replisome passage through the cohesin ring or by transfer of cohesin behind the replication fork by replisome components 5 . Unexpectedly, by visualising single replication forks colliding with pre-loaded cohesin complexes, we find that cohesin is pushed by the replisome to where a converging replisome is met. Whilst the converging replisomes are removed during DNA replication termination, cohesin remains on nascent DNA. We demonstrate that these cohesin molecules tether the newly replicated sister DNAs together. Our results support a new model where sister chromatid cohesion is established during DNA replication termination, providing important insight into the molecular mechanism of cohesion establishment.
Title: Sister chromatid cohesion establishment during DNA replication termination
Description:
Abstract The cohesin complex tethers sister chromatids together from the moment they are generated in S-phase until their separation in anaphase 1,2 .
This fundamental phenomenon, called sister chromatid cohesion, underpins orderly chromosome segregation.
The replisome complex coordinates cohesion establishment with replication of parental DNA 3 .
Cohesion can be established by cohesin complexes bound to DNA before replication 4,5 , but how replisome interaction with pre-loaded cohesin complexes results in cohesion is not known.
Prevailing models suggest cohesion is established by replisome passage through the cohesin ring or by transfer of cohesin behind the replication fork by replisome components 5 .
Unexpectedly, by visualising single replication forks colliding with pre-loaded cohesin complexes, we find that cohesin is pushed by the replisome to where a converging replisome is met.
Whilst the converging replisomes are removed during DNA replication termination, cohesin remains on nascent DNA.
We demonstrate that these cohesin molecules tether the newly replicated sister DNAs together.
Our results support a new model where sister chromatid cohesion is established during DNA replication termination, providing important insight into the molecular mechanism of cohesion establishment.

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