Checkpoint-mediated control of replicating chromosomes is essential for preventing cancer. In yeast, Rad53 kinase protects stalled replication forks from pathological rearrangements, To characterize the mechanisms controlling fork integrity, we analyzed replication intermediates formed in response to replication blocks using electron microscopy, At the forks, wild-type cells accumulate short single-stranded regions, which likely causes checkpoint activation, whereas rad53 mutants exhibit extensive single-stranded gaps and hemi-replicated intermediates, consistent with a tagging-strand synthesis defect. Further, rad53 cells accumulate Holliday junctions through fork reversal. We speculate that, in checkpoint mutants, abnormal replication intermediates begin to form because of uncoordinated replication and are further processed by unscheduled recombination pathways, causing genome instability.

Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects / J.M. Sogo, M. Lopes, M. Foiani. - In: SCIENCE. - ISSN 0036-8075. - 297:5581(2002), pp. 599-602. [10.1126/science.1074023]

Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects

M. Lopes;M. Foiani
Ultimo
2002

Abstract

Checkpoint-mediated control of replicating chromosomes is essential for preventing cancer. In yeast, Rad53 kinase protects stalled replication forks from pathological rearrangements, To characterize the mechanisms controlling fork integrity, we analyzed replication intermediates formed in response to replication blocks using electron microscopy, At the forks, wild-type cells accumulate short single-stranded regions, which likely causes checkpoint activation, whereas rad53 mutants exhibit extensive single-stranded gaps and hemi-replicated intermediates, consistent with a tagging-strand synthesis defect. Further, rad53 cells accumulate Holliday junctions through fork reversal. We speculate that, in checkpoint mutants, abnormal replication intermediates begin to form because of uncoordinated replication and are further processed by unscheduled recombination pathways, causing genome instability.
DNA-replication; damage; yeast; phosphorylation; progression; activation; pathway; origins; kinase
Settore BIO/11 - Biologia Molecolare
Article (author)
File in questo prodotto:
File Dimensione Formato  
31 2002 Sogo Science.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 649.22 kB
Formato Adobe PDF
649.22 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/659557
Citazioni
  • ???jsp.display-item.citation.pmc??? 384
  • Scopus 669
  • ???jsp.display-item.citation.isi??? 650
social impact