UV stalled replication forks restart by re-priming in human fibroblasts.

Abstract:

:Restarting stalled replication forks is vital to avoid fatal replication errors. Previously, it was demonstrated that hydroxyurea-stalled replication forks rescue replication either by an active restart mechanism or by new origin firing. To our surprise, using the DNA fibre assay, we only detect a slightly reduced fork speed on a UV-damaged template during the first hour after UV exposure, and no evidence for persistent replication fork arrest. Interestingly, no evidence for persistent UV-induced fork stalling was observed even in translesion synthesis defective, Polη(mut) cells. In contrast, using an assay to measure DNA molecule elongation at the fork, we observe that continuous DNA elongation is severely blocked by UV irradiation, particularly in UV-damaged Polη(mut) cells. In conclusion, our data suggest that UV-blocked replication forks restart effectively through re-priming past the lesion, leaving only a small gap opposite the lesion. This allows continuation of replication on damaged DNA. If left unfilled, the gaps may collapse into DNA double-strand breaks that are repaired by a recombination pathway, similar to the fate of replication forks collapsed after hydroxyurea treatment.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Elvers I,Johansson F,Groth P,Erixon K,Helleday T

doi

10.1093/nar/gkr420

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

7049-57

issue

16

eissn

0305-1048

issn

1362-4962

pii

gkr420

journal_volume

39

pub_type

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