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Nuclear envelope integrity, DNA replication, damage repair and genome stability

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Abstract

The nuclear envelope (NE) not only shields the genetic material inside the nucleus, maintains the dynamic shapes of nucleus, and regulates nuclear exchange with cytosol, but also participates in DNA replication, damage repair and transcription regulation. The loss of NE integrity, as observed in various diseases, has been shown to cause genome instability as a result of genetic material leaking into the cytoplasm. An underestimated but critically important factor of genome integrity is the role of NE components that involve in DNA replication and damage repair. In this review, we summarize the triggers of NE loss and its cellular consequences by focusing on the interactions between NE components and DNA replication and repair factors. Studies on how NE mediates DNA replication and damage repair could shed light on the diagnosis and treatment of human diseases such as cancer and laminopathy.

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Abbreviations

A-NHEJ:

Alternative non-homologous end joining

ATM:

Ataxia-telangiectasia mutated protein

ATR:

Ataxia telangiectasia and Rad3-related protein

BAF:

Barrier-to-autointegration factor

cGAS:

Cyclic GMP-AMP synthase

ChIP:

Chromatin immunoprecipitation

CHMP:

Charged multivesicular body protein

DamID:

DNA adenine methyltransferase identification

DNA:

Deoxyribonucleic acid

DNA-PK:

DNA-dependent protein kinase

DSBs:

Double-strand breaks

ESCRT:

Endosomal sorting complexes required for transport

ER:

Endoplasmic reticulum

FANCD2:

Fanconi anemia group D2 protein

HGPS:

Hutchinson-Gilford progeria syndrome

HR:

Homologous recombination

ICL:

Interstrand cross-links

INM:

Inner nuclear membrane

LADs:

Lamina-associated domains

LEM:

Lap-Emerin-Man domain protein

LINC:

Linker of nucleoskeleton and cytoskeleton

NE:

Nuclear envelope

NEBD:

Nuclear envelope breakdown

NHEJ:

Non-homologous end joining

NPC:

Nuclear pore complexes

ONM:

Outer nuclear membrane

PCNA:

Proliferating cell nuclear antigen

RFC:

Replication factor complex

RPA:

Replication protein A

SSA:

Single-strand annealing

STING:

Stimulator of interferon genes

STUbL:

SUMO targeted ubiquitin ligase

SUMO:

Small ubiquitin-like modifier

TREX1:

Three-prime repair exonuclease 1

UbcH7:

Ubiquitin-conjugating enzyme H7

XPA:

Xeroderma pigmentosum group A

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Acknowledgements

We would like to thank the members of the Deng and Qin laboratories for helpful discussions. We apologize to those whose excellent work could not be cited directly in this review due to space limitations. This work is supported by the Guangdong Basic and Applied Basic Research Foundation (2020A1515110542, to L.D.), National Natural Science Foundation of China (31970752, to P.Q.), Science, Technology and Innovation Commission of Shenzhen Municipality (JSGG20191129110812, to P.Q.), and Shenzhen Bay Laboratory Open Fund (SZBL2020090501004, to P.Q.).

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  1. Shenzhen Bay Laboratory, Shenzhen, China

    Wenjun Pu & Lin Deng

  2. Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China

    Haihui Zhang & Peiwu Qin

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  1. Wenjun Pu
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  2. Haihui Zhang
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Correspondence to Lin Deng.

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Pu, W., Zhang, H., Qin, P. et al. Nuclear envelope integrity, DNA replication, damage repair and genome stability. GENOME INSTAB. DIS. 2, 102–114 (2021). https://doi.org/10.1007/s42764-021-00039-w

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