Lamin A/C promotes DNA base excision repair

Nucleic Acids Res. 2019 Dec 16;47(22):11709-11728. doi: 10.1093/nar/gkz912.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging, Premature / genetics
  • Aging, Premature / metabolism
  • Animals
  • Cells, Cultured
  • DNA Damage / physiology
  • DNA Repair / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Lamin Type A / physiology*
  • Mice
  • Microarray Analysis
  • Nuclear Lamina / genetics
  • Nuclear Lamina / metabolism
  • Oxidative Stress / genetics
  • Progeria / genetics


  • LMNA protein, human
  • Lamin Type A