High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing. / Macheret, Morgane; Bhowmick, Rahul; Sobkowiak, Katarzyna; Padayachy, Laura; Mailler, Jonathan; Hickson, Ian D.; Halazonetis, Thanos D.

In: Cell Research, Vol. 30, 2020, p. 997–1008.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Macheret, M, Bhowmick, R, Sobkowiak, K, Padayachy, L, Mailler, J, Hickson, ID & Halazonetis, TD 2020, 'High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing', Cell Research, vol. 30, pp. 997–1008. https://doi.org/10.1038/s41422-020-0358-x

APA

Macheret, M., Bhowmick, R., Sobkowiak, K., Padayachy, L., Mailler, J., Hickson, I. D., & Halazonetis, T. D. (2020). High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing. Cell Research, 30, 997–1008. https://doi.org/10.1038/s41422-020-0358-x

Vancouver

Macheret M, Bhowmick R, Sobkowiak K, Padayachy L, Mailler J, Hickson ID et al. High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing. Cell Research. 2020;30:997–1008. https://doi.org/10.1038/s41422-020-0358-x

Author

Macheret, Morgane ; Bhowmick, Rahul ; Sobkowiak, Katarzyna ; Padayachy, Laura ; Mailler, Jonathan ; Hickson, Ian D. ; Halazonetis, Thanos D. / High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing. In: Cell Research. 2020 ; Vol. 30. pp. 997–1008.

Bibtex

@article{3f835e1826f74d09b7db845f9babfae7,
title = "High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing",
abstract = "DNA replication stress, a feature of human cancers, often leads to instability at specific genomic loci, such as the common fragile sites (CFSs). Cells experiencing DNA replication stress may also exhibit mitotic DNA synthesis (MiDAS). To understand the physiological function of MiDAS and its relationship to CFSs, we mapped, at high resolution, the genomic sites of MiDAS in cells treated with the DNA polymerase inhibitor aphidicolin. Sites of MiDAS were evident as well-defined peaks that were largely conserved between cell lines and encompassed all known CFSs. The MiDAS peaks mapped within large, transcribed, origin-poor genomic regions. In cells that had been treated with aphidicolin, these regions remained unreplicated even in late S phase; MiDAS then served to complete their replication after the cells entered mitosis. Interestingly, leading and lagging strand synthesis were uncoupled in MiDAS, consistent with MiDAS being a form of break-induced replication, a repair mechanism for collapsed DNA replication forks. Our results provide a better understanding of the mechanisms leading to genomic instability at CFSs and in cancer cells.",
author = "Morgane Macheret and Rahul Bhowmick and Katarzyna Sobkowiak and Laura Padayachy and Jonathan Mailler and Hickson, {Ian D.} and Halazonetis, {Thanos D.}",
year = "2020",
doi = "10.1038/s41422-020-0358-x",
language = "English",
volume = "30",
pages = "997–1008",
journal = "Cell Research",
issn = "1001-0602",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing

AU - Macheret, Morgane

AU - Bhowmick, Rahul

AU - Sobkowiak, Katarzyna

AU - Padayachy, Laura

AU - Mailler, Jonathan

AU - Hickson, Ian D.

AU - Halazonetis, Thanos D.

PY - 2020

Y1 - 2020

N2 - DNA replication stress, a feature of human cancers, often leads to instability at specific genomic loci, such as the common fragile sites (CFSs). Cells experiencing DNA replication stress may also exhibit mitotic DNA synthesis (MiDAS). To understand the physiological function of MiDAS and its relationship to CFSs, we mapped, at high resolution, the genomic sites of MiDAS in cells treated with the DNA polymerase inhibitor aphidicolin. Sites of MiDAS were evident as well-defined peaks that were largely conserved between cell lines and encompassed all known CFSs. The MiDAS peaks mapped within large, transcribed, origin-poor genomic regions. In cells that had been treated with aphidicolin, these regions remained unreplicated even in late S phase; MiDAS then served to complete their replication after the cells entered mitosis. Interestingly, leading and lagging strand synthesis were uncoupled in MiDAS, consistent with MiDAS being a form of break-induced replication, a repair mechanism for collapsed DNA replication forks. Our results provide a better understanding of the mechanisms leading to genomic instability at CFSs and in cancer cells.

AB - DNA replication stress, a feature of human cancers, often leads to instability at specific genomic loci, such as the common fragile sites (CFSs). Cells experiencing DNA replication stress may also exhibit mitotic DNA synthesis (MiDAS). To understand the physiological function of MiDAS and its relationship to CFSs, we mapped, at high resolution, the genomic sites of MiDAS in cells treated with the DNA polymerase inhibitor aphidicolin. Sites of MiDAS were evident as well-defined peaks that were largely conserved between cell lines and encompassed all known CFSs. The MiDAS peaks mapped within large, transcribed, origin-poor genomic regions. In cells that had been treated with aphidicolin, these regions remained unreplicated even in late S phase; MiDAS then served to complete their replication after the cells entered mitosis. Interestingly, leading and lagging strand synthesis were uncoupled in MiDAS, consistent with MiDAS being a form of break-induced replication, a repair mechanism for collapsed DNA replication forks. Our results provide a better understanding of the mechanisms leading to genomic instability at CFSs and in cancer cells.

U2 - 10.1038/s41422-020-0358-x

DO - 10.1038/s41422-020-0358-x

M3 - Journal article

C2 - 32561860

AN - SCOPUS:85086571711

VL - 30

SP - 997

EP - 1008

JO - Cell Research

JF - Cell Research

SN - 1001-0602

ER -

ID: 244611878