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Molecular details of parental histone redistribution at DNA replication

Determine the molecular mechanism by which parental histones (and their epigenetic marks) are redistributed between leading and lagging strands during DNA replication, including whether and how toggling between strands occurs and the role of the fork protection complex in governing this redistribution.

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Background

During replication, parental nucleosomes carrying epigenetic marks are split between daughter DNA molecules, leading to dilution of marks. The paper models this process via a distribution bias parameter pb to explore different local patterns of mark retention.

While global symmetry (roughly half of marked histones inherited per daughter) is supported experimentally, the authors note that the molecular details of how parental histones are allocated or toggled between leading and lagging strands remain elusive, highlighting an explicitly stated unresolved mechanistic question.

References

Molecular details of the transfer remain elusive, but there is some evidence suggesting histones to be "toggled" between leading and lagging strands in a fairly regular manner facilitated by the fork protection complex [40].

— A self-organised liquid reaction container for cellular memory (2412.15394 - Mukherjee et al., 19 Dec 2024) in Section “Restoration of epigenetic marks in one cell generation,” paragraph introducing distribution bias pb (near reference [40])