# Roles of DNA Damage Response Pathway in the Regulation of the Nuclear Envelope

**Authors:** Yasunao Kamikawa, Zuqian Wu, Kenshiro Fujise, Kazunori Imaizumi, Atsushi Saito

PMC · DOI: 10.3390/cimb48030240 · 2026-02-24

## TL;DR

This paper reviews how DNA damage response pathways, especially the ATR kinase, regulate the nuclear envelope.

## Contribution

The paper highlights ATR's novel role in linking DNA damage to nuclear envelope regulation.

## Key findings

- NE rupture can cause DNA damage and is linked to DDR pathways.
- ATR kinase is a key regulator in DNA damage-induced NE rupture.
- DDR pathways play a central role in maintaining NE integrity.

## Abstract

The nuclear envelope (NE) functions as a barrier between the cytoplasm and nucleus. Over the past decade, NE has revealed unexpectedly divergent structural alterations. NE rupture triggers the uncontrollable exchange of macromolecules across the NE and potentially causes DNA damage. Conversely, a recent study demonstrated that DNA damage induces NE rupture and that one of the major kinases in the DNA damage response (DDR) pathway, ataxia telangiectasia and Rad3-related protein, ATR, is a key molecule in these events. Here, we review the role of the DDR pathway in NE regulation, with a focus mainly on ATR.

## Linked entities

- **Genes:** ATR (ATR checkpoint kinase) [NCBI Gene 545]
- **Proteins:** ATR (ATR checkpoint kinase)

## Full-text entities

- **Genes:** Prkdc (protein kinase, DNA activated, catalytic polypeptide) [NCBI Gene 19090] {aka DNA-PKcs, DNAPDcs, DNAPK, DNPK1, DOXNPH, HYRC1}, Diaph3 (diaphanous related formin 3) [NCBI Gene 56419] {aka 4930417P13Rik, Dia2, Diap3, Drf3, p134MDia2}, Xpo6 (exportin 6) [NCBI Gene 74204] {aka 2610005L19Rik, C230091E20Rik, Ranbp20, exp6, mKIAA0370}, Chek1 (checkpoint kinase 1) [NCBI Gene 12649] {aka Chk1, rad27}, Rb1 (RB transcriptional corepressor 1) [NCBI Gene 19645] {aka Rb, Rb-1, p110-RB1, pRb, pp105}, Setdb1 (SET domain, bifurcated 1) [NCBI Gene 84505] {aka ESET, KMT1E, mKIAA0067}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, Lmna (lamin A) [NCBI Gene 16905] {aka Dhe}, Ipo9 (importin 9) [NCBI Gene 226432] {aka 0710008K06Rik, Imp9, Ranbp9}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, Atr (ataxia telangiectasia and Rad3 related) [NCBI Gene 245000], Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, Rassf1 (Ras association (RalGDS/AF-6) domain family member 1) [NCBI Gene 56289] {aka 123F2, NORE2A, RDA32, REH3P21, Rassf1A, Rassf1B}, Chmp7 (charged multivesicular body protein 7) [NCBI Gene 105513] {aka 4930596K11Rik, 6330407G04Rik}, Usp39 (ubiquitin specific peptidase 39) [NCBI Gene 28035] {aka CGI-21, D6Wsu157e, SAD1}, Pcna (proliferating cell nuclear antigen) [NCBI Gene 18538], Lemd3 (LEM domain containing 3) [NCBI Gene 380664] {aka Man1}, Cdk1 (cyclin dependent kinase 1) [NCBI Gene 12534] {aka Cdc2, Cdc2a, p34<CDC2>}, Trim28 (tripartite motif-containing 28) [NCBI Gene 21849] {aka KAP-1, KRIP-1, MommeD9, Tif1b, Tif1beta}, Ar (androgen receptor) [NCBI Gene 11835] {aka Tfm}, Cgas (cyclic GMP-AMP synthase) [NCBI Gene 214763] {aka E330016A19Rik, Mb21d1}, Lmnb2 (lamin B2) [NCBI Gene 16907], Hp (haptoglobin) [NCBI Gene 15439] {aka HP-1, preHP2}, Chek2 (checkpoint kinase 2) [NCBI Gene 50883] {aka CHK2, Cds1, HUCDS1, Rad53}, Flna (filamin, alpha) [NCBI Gene 192176] {aka ABP-280, Dilp2, F730004A14Rik, Fln1, GENA 379, filamin-1}, Lmnb1 (lamin B1) [NCBI Gene 16906], Emd (emerin) [NCBI Gene 13726] {aka Sta}, baf (b-associated fitness) [NCBI Gene 12016], Syne2 (spectrin repeat containing, nuclear envelope 2) [NCBI Gene 319565] {aka 6820443O06Rik, Cpfl8, D12Ertd777e, KASH2, NUA, Nesp2g}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Slc25a4 (solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 4) [NCBI Gene 11739] {aka Ant1, mANC1}
- **Diseases:** cardiac hypertrophy (MESH:D006332), cerebral hemorrhage (MESH:D002543), progeroid syndrome (MESH:C536423), soft tissue sarcoma (MESH:D012509), injury to (MESH:D014947), colorectal cancer (MESH:D015179), neurodegenerative diseases (MESH:D019636), hepatocellular carcinoma (MESH:D006528), NE (MESH:C564596), cancer (MESH:D009369), NE rupture (MESH:D012421), HGPS (MESH:D011371), inflammatory (MESH:D007249), breast cancer (MESH:D001943)
- **Chemicals:** Thr (MESH:D013912), Gln (MESH:D005973), Ser (MESH:D012694), Progerin (-), lipid (MESH:D008055), oxaliplatin (MESH:D000077150), reactive oxygen species (MESH:D017382)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** A to Ala, A133S, R62D

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025569/full.md

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Source: https://tomesphere.com/paper/PMC13025569