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| Status |
Public on Sep 30, 2020 |
| Title |
Lamin A/C promotes DNA base excision repair (human arrays) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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, including the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). 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. The mechanism involves impairment of the APE1 and POLβ enzyme activities in BER. Also, Lmna null mouse fibroblasts displayed reduced expression of several core BER enzymes (PARP1, LIG3, and POLβ). Moreover, the robustness of APE1 and POLβ activities and the rate of BER were enhanced by lamin A/C-augmented poly(ADP-ribose) polymer formation (PARylation). Finally, we report that HGPS fibroblasts are defective in BER. Collectively, our results provide novel insights into the functional interplay between the nuclear lamina and cellular defenses against oxidative DNA damage, with implications for human cancer and aging.
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| Overall design |
Microarray analysis of cell lines from Hutchinson-Gilford progeria syndrome (HGPS)-affected individuals and a clinically unaffected parent (three patient-parent pairs, three replicates per condition) for a total of eighteen microarray samples.
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| Contributor(s) |
Maynard S, Keijzers G, Akbari M, Morevati M, Scheibye-Knudsen M, Gonzalo S, Bartek J, Bohr VA |
| Citation(s) |
31647095, 36099415 |
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| Submission date |
Dec 28, 2018 |
| Last update date |
Oct 21, 2022 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (18)
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| GSM3534599 |
C1ag3257-1: Fibroblast_Ctr for HGPS affected-1_rep.1 |
| GSM3534600 |
C1ag3257-2: Fibroblast_Ctr for HGPS affected-1_rep.2 |
| GSM3534601 |
C1ag3257-3: Fibroblast_Ctr for HGPS affected-1_rep.3 |
| GSM3534602 |
D1ag3199-1: Fibroblast_HGPS affected-1_rep. 1 |
| GSM3534603 |
D1ag3199-2: Fibroblast_HGPS affected-1_rep. 2 |
| GSM3534604 |
D1ag3199-3: Fibroblast_HGPS affected-1_rep. 3 |
| GSM3534605 |
C3ag3512-1: Fibroblast_Ctr for HGPS affected-2_rep.1 |
| GSM3534606 |
C3ag3512-2: Fibroblast_Ctr for HGPS affected-2_rep.2 |
| GSM3534607 |
C3ag3512-3: Fibroblast_Ctr for HGPS affected-2_rep.3 |
| GSM3534608 |
D3ag3513-1: Fibroblast_HGPS affected-2_rep. 1 |
| GSM3534609 |
D3ag3513-2: Fibroblast_HGPS affected-2_rep. 2 |
| GSM3534610 |
D3ag3513-3: Fibroblast_HGPS affected-2_rep. 3 |
| GSM3534611 |
C4ag6299-1: Fibroblast_Ctr for HGPS affected-3_rep.1 |
| GSM3534612 |
C4ag6299-2: Fibroblast_Ctr for HGPS affected-3_rep.2 |
| GSM3534613 |
C4ag6299-3: Fibroblast_Ctr for HGPS affected-3_rep.3 |
| GSM3534614 |
D4ag6917-1: Fibroblast_HGPS affected-3_rep. 1 |
| GSM3534615 |
D4ag6917-2: Fibroblast_HGPS affected-3_rep. 2 |
| GSM3534616 |
D4ag6917-3: Fibroblast_HGPS affected-3_rep. 3 |
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| This SubSeries is part of SuperSeries: |
| GSE124467 |
Lamin A/C promotes DNA base excision repair |
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| Relations |
| BioProject |
PRJNA512096 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE124465_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE124465_data_worksheets.xlsx |
30.2 Mb |
(ftp)(http) |
XLSX |
| Processed data included within Sample table |
| Processed data are available on Series record |
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