Telomere replication—When the going gets tough

Susanna Stroik, Eric A. Hendrickson

Research output: Contribution to journalArticlepeer-review

Abstract

Telomeres consist of repetitive tracts of DNA that shield a chromosome's contents from erosion and replicative attrition. However, telomeres are also late-replicating regions of the genome in which a myriad of replicative obstructions reside. The obstacles contained within telomeres, as well as their genomic location, drive replicative stalling and subsequent fork collapse in these regions. Consequently, large scale deletions, under-replicated DNA, translocations, and fusion events arise following telomere replication failure. Further, under-replicated DNA and telomere fusions that are permitted to enter mitosis will produce mitotic DNA bridges — known drivers of genetic loss and chromothripsis. Thus, aberrant telomere replication promotes genomic instability, which, in turn leads either to cellular death, senescence or oncogenic transformation. The importance of these issues for organismal well-being necessitates a need for resolute telomere maintenance. Here, we describe recent advances in identifying and understanding the molecular mechanisms that are in place in human cells to escort the replisome through the telomere's unwieldy structures and repetitive sequences. Finally, we review the pathways that combat the deleterious outcomes that occur when telomeric replication forks do collapse.

Original languageEnglish (US)
Article number102875
JournalDNA Repair
Volume94
DOIs
StatePublished - Oct 2020

Bibliographical note

Funding Information:
Work in the Hendrickson laboratory was supported in part by grants from the NIH ( GM088351 ) and the NCI ( CA190492 ). EAH thanks Dr. Anja K. Bielinsky for her comments on the manuscript.

Publisher Copyright:
© 2020

Keywords

  • Chromatin bridges
  • Homology-dependent repair
  • Replication
  • Restart
  • Stalled forks
  • Telomere

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Review

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