Lamin A/C promotes DNA base excision repair

Research output: Contribution to journalJournal articleResearchpeer-review

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Lamin A/C promotes DNA base excision repair. / Maynard, Scott; Keijzers, Guido; Akbari, Mansour; Ezra, Michael Ben; Hall, Arnaldur; Morevati, Marya; Scheibye-Knudsen, Morten; Gonzalo, Susana; Bartek, Jiri; Bohr, Vilhelm A.

In: Nucleic Acids Research, Vol. 47, No. 22, 2019, p. 11709–11728.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Maynard, S, Keijzers, G, Akbari, M, Ezra, MB, Hall, A, Morevati, M, Scheibye-Knudsen, M, Gonzalo, S, Bartek, J & Bohr, VA 2019, 'Lamin A/C promotes DNA base excision repair', Nucleic Acids Research, vol. 47, no. 22, pp. 11709–11728. https://doi.org/10.1093/nar/gkz912

APA

Maynard, S., Keijzers, G., Akbari, M., Ezra, M. B., Hall, A., Morevati, M., ... Bohr, V. A. (2019). Lamin A/C promotes DNA base excision repair. Nucleic Acids Research, 47(22), 11709–11728. https://doi.org/10.1093/nar/gkz912

Vancouver

Maynard S, Keijzers G, Akbari M, Ezra MB, Hall A, Morevati M et al. Lamin A/C promotes DNA base excision repair. Nucleic Acids Research. 2019;47(22):11709–11728. https://doi.org/10.1093/nar/gkz912

Author

Maynard, Scott ; Keijzers, Guido ; Akbari, Mansour ; Ezra, Michael Ben ; Hall, Arnaldur ; Morevati, Marya ; Scheibye-Knudsen, Morten ; Gonzalo, Susana ; Bartek, Jiri ; Bohr, Vilhelm A. / Lamin A/C promotes DNA base excision repair. In: Nucleic Acids Research. 2019 ; Vol. 47, No. 22. pp. 11709–11728.

Bibtex

@article{ef877924b1bb4b81885a180e897f11e4,
title = "Lamin A/C promotes DNA base excision repair",
abstract = "The A-type lamins (lamin A/C), encoded by the LMNA gene, are important structural components of the nuclear lamina. LMNA mutations lead to degenerative disorders known as laminopathies, including the premature aging disease Hutchinson-Gilford progeria syndrome. In addition, altered lamin A/C expression is found in various cancers. Reports indicate that lamin A/C plays a role in DNA double strand break repair, but a role in DNA base excision repair (BER) has not been described. We provide evidence for reduced BER efficiency in lamin A/C-depleted cells (Lmna null MEFs and lamin A/C-knockdown U2OS). The mechanism involves impairment of the APE1 and POLβ BER activities, partly effectuated by associated reduction in poly-ADP-ribose chain formation. Also, Lmna null MEFs displayed reduced expression of several core BER enzymes (PARP1, LIG3 and POLβ). Absence of Lmna led to accumulation of 8-oxoguanine (8-oxoG) lesions, and to an increased frequency of substitution mutations induced by chronic oxidative stress including GC>TA transversions (a fingerprint of 8-oxoG:A mismatches). Collectively, our results provide novel insights into the functional interplay between the nuclear lamina and cellular defenses against oxidative DNA damage, with implications for cancer and aging.",
author = "Scott Maynard and Guido Keijzers and Mansour Akbari and Ezra, {Michael Ben} and Arnaldur Hall and Marya Morevati and Morten Scheibye-Knudsen and Susana Gonzalo and Jiri Bartek and Bohr, {Vilhelm A}",
note = "Published by Oxford University Press on behalf of Nucleic Acids Research 2019.",
year = "2019",
doi = "10.1093/nar/gkz912",
language = "English",
volume = "47",
pages = "11709–11728",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "22",

}

RIS

TY - JOUR

T1 - Lamin A/C promotes DNA base excision repair

AU - Maynard, Scott

AU - Keijzers, Guido

AU - Akbari, Mansour

AU - Ezra, Michael Ben

AU - Hall, Arnaldur

AU - Morevati, Marya

AU - Scheibye-Knudsen, Morten

AU - Gonzalo, Susana

AU - Bartek, Jiri

AU - Bohr, Vilhelm A

N1 - Published by Oxford University Press on behalf of Nucleic Acids Research 2019.

PY - 2019

Y1 - 2019

N2 - The A-type lamins (lamin A/C), encoded by the LMNA gene, are important structural components of the nuclear lamina. LMNA mutations lead to degenerative disorders known as laminopathies, including the premature aging disease Hutchinson-Gilford progeria syndrome. In addition, altered lamin A/C expression is found in various cancers. Reports indicate that lamin A/C plays a role in DNA double strand break repair, but a role in DNA base excision repair (BER) has not been described. We provide evidence for reduced BER efficiency in lamin A/C-depleted cells (Lmna null MEFs and lamin A/C-knockdown U2OS). The mechanism involves impairment of the APE1 and POLβ BER activities, partly effectuated by associated reduction in poly-ADP-ribose chain formation. Also, Lmna null MEFs displayed reduced expression of several core BER enzymes (PARP1, LIG3 and POLβ). Absence of Lmna led to accumulation of 8-oxoguanine (8-oxoG) lesions, and to an increased frequency of substitution mutations induced by chronic oxidative stress including GC>TA transversions (a fingerprint of 8-oxoG:A mismatches). Collectively, our results provide novel insights into the functional interplay between the nuclear lamina and cellular defenses against oxidative DNA damage, with implications for cancer and aging.

AB - The A-type lamins (lamin A/C), encoded by the LMNA gene, are important structural components of the nuclear lamina. LMNA mutations lead to degenerative disorders known as laminopathies, including the premature aging disease Hutchinson-Gilford progeria syndrome. In addition, altered lamin A/C expression is found in various cancers. Reports indicate that lamin A/C plays a role in DNA double strand break repair, but a role in DNA base excision repair (BER) has not been described. We provide evidence for reduced BER efficiency in lamin A/C-depleted cells (Lmna null MEFs and lamin A/C-knockdown U2OS). The mechanism involves impairment of the APE1 and POLβ BER activities, partly effectuated by associated reduction in poly-ADP-ribose chain formation. Also, Lmna null MEFs displayed reduced expression of several core BER enzymes (PARP1, LIG3 and POLβ). Absence of Lmna led to accumulation of 8-oxoguanine (8-oxoG) lesions, and to an increased frequency of substitution mutations induced by chronic oxidative stress including GC>TA transversions (a fingerprint of 8-oxoG:A mismatches). Collectively, our results provide novel insights into the functional interplay between the nuclear lamina and cellular defenses against oxidative DNA damage, with implications for cancer and aging.

U2 - 10.1093/nar/gkz912

DO - 10.1093/nar/gkz912

M3 - Journal article

C2 - 31647095

VL - 47

SP - 11709

EP - 11728

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 22

ER -

ID: 229437597