May 1, 2024Nature Structural & Molecular BiologyOpen Access

Deregulated DNA ADP-ribosylation impairs telomere replication

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Authors

AWAnne R. WondisfordUPMC Hillman Cancer Center JLJunyeop LeeCancer Genetics (United States)RLRobert LuUniversity of California, Berkeley

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Implication

Molecular analysis demonstrates that persistent DNA ADP-ribosylation disrupts telomere replication in cellular models, highlighting the role of TARG1 in sustaining genome stability.

Key Points

Telomere shortening and replication defects arise when DNA ADP-ribosylation turnover is disrupted, which impairs lagging telomere strand synthesis at unligated Okazaki fragments.
Genetic deficiency of TARG1 prevents removal of PARP1-catalyzed DNA ADP-ribosylation on Okazaki fragments and single-stranded overhangs, triggering cumulative telomere shortening.
These findings highlight the necessity of balanced DNA ADP-ribosylation turnover for sustained genome stability; cell-based model limits warrant further preclinical replication work.

Cite This Study

Wondisford et al. (2024) studied this question.

synapsesocial.com/papers/68e6c03bb6db64358763fb7f https://doi.org/10.1038/s41594-024-01279-6

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Implication

Molecular analysis demonstrates that persistent DNA ADP-ribosylation disrupts telomere replication in cellular models, highlighting the role of TARG1 in sustaining genome stability.

Deregulated DNA ADP-ribosylation impairs telomere replication

Discussion

Member takes

Implication

Key Points

Cite This Study

Deregulated DNA ADP-ribosylation impairs telomere replication

Discussion

Member takes

Implication

Key Points

Cite This Study

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