DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity

Noam Diamant, Ayal Hendel, Ilan Vered, Thomas Carell, Thomas Reißner, Niels De Wind, Nicholas Geacintov, Zvi Livneh

Research output: Contribution to journalArticle

Abstract

Translesion DNA synthesis (TLS) employs low-fidelity DNA polymerases to bypass replication-blocking lesions, and being associated with chromosomal replication was presumed to occur in the S phase of the cell cycle. Using immunostaining with anti-replication protein A antibodies, we show that in UV-irradiated mammalian cells, chromosomal single-stranded gaps formed in S phase during replication persist into the G2 phase of the cell cycle, where their repair is completed depending on DNA polymerase ζ and Rev1. Analysis of TLS using a high-resolution gapped-plasmid assay system in cell populations enriched by centrifugal elutriation for specific cell cycle phases showed that TLS operates both in S and G2. Moreover, the mutagenic specificity of TLS in G2 was different from S, and in some cases overall mutation frequency was higher. These results suggest that TLS repair of single-stranded gaps caused by DNA lesions can lag behind chromosomal replication, is separable from it, and occurs both in the S and G2 phases of the cell cycle. Such a mechanism may function to maintain efficient replication, which can progress despite the presence of DNA lesions, with TLS lagging behind and patching regions of discontinuity.

Original languageEnglish (US)
Pages (from-to)170-180
Number of pages11
JournalNucleic Acids Research
Volume40
Issue number1
DOIs
StatePublished - Jan 2012

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G2 Phase
S Phase
DNA Damage
Cell Cycle
DNA
DNA-Directed DNA Polymerase
Replication Protein A
Mutation Rate
DNA Repair
Plasmids
Antibodies
Population

ASJC Scopus subject areas

  • Genetics

Cite this

Diamant, N., Hendel, A., Vered, I., Carell, T., Reißner, T., De Wind, N., ... Livneh, Z. (2012). DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity. Nucleic Acids Research, 40(1), 170-180. https://doi.org/10.1093/nar/gkr596

DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity. / Diamant, Noam; Hendel, Ayal; Vered, Ilan; Carell, Thomas; Reißner, Thomas; De Wind, Niels; Geacintov, Nicholas; Livneh, Zvi.

In: Nucleic Acids Research, Vol. 40, No. 1, 01.2012, p. 170-180.

Research output: Contribution to journalArticle

Diamant, N, Hendel, A, Vered, I, Carell, T, Reißner, T, De Wind, N, Geacintov, N & Livneh, Z 2012, 'DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity', Nucleic Acids Research, vol. 40, no. 1, pp. 170-180. https://doi.org/10.1093/nar/gkr596
Diamant, Noam ; Hendel, Ayal ; Vered, Ilan ; Carell, Thomas ; Reißner, Thomas ; De Wind, Niels ; Geacintov, Nicholas ; Livneh, Zvi. / DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity. In: Nucleic Acids Research. 2012 ; Vol. 40, No. 1. pp. 170-180.
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