Crosstalk between SUMOylation and ubiquitylation controls DNA end resection by maintaining MRE11 homeostasis on chromatin

Zhang, Tao; Yang, Han; Zhou, Zenan; Bai, Yongtai; Wang, Jiadong; Wang, Weibin

doi:10.1038/s41467-022-32920-x

Cited by 11 publications

(2 citation statements)

References 63 publications

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“…MRE11A is SUMOylated following DSB generation [ 44 , 59–61 ]. SUMOylation stabilises MRE11A by preventing its ubiquitination and degradation [ 61 ]. SUMOylation also stabilises the NBS1 interactor hSSB1 (single-stranded DNA-binding protein 1) enhancing ATM recruitment to DSBs [ 62 ].…”

Section: Dna End Resectionmentioning

confidence: 99%

SUMO and the DNA damage response

Bhachoo,

Garvin

2024

Biochemical Society Transactions

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The preservation of genome integrity requires specialised DNA damage repair (DDR) signalling pathways to respond to each type of DNA damage. A key feature of DDR is the integration of numerous post-translational modification signals with DNA repair factors. These modifications influence DDR factor recruitment to damaged DNA, activity, protein-protein interactions, and ultimately eviction to enable access for subsequent repair factors or termination of DDR signalling. SUMO1-3 (small ubiquitin-like modifier 1-3) conjugation has gained much recent attention. The SUMO-modified proteome is enriched with DNA repair factors. Here we provide a snapshot of our current understanding of how SUMO signalling impacts the major DNA repair pathways in mammalian cells. We highlight repeating themes of SUMO signalling used throughout DNA repair pathways including the assembly of protein complexes, competition with ubiquitin to promote DDR factor stability and ubiquitin-dependent degradation or extraction of SUMOylated DDR factors. As SUMO ‘addiction’ in cancer cells is protective to genomic integrity, targeting components of the SUMO machinery to potentiate DNA damaging therapy or exacerbate existing DNA repair defects is a promising area of study.

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Section: Dna End Resectionmentioning

confidence: 99%

SUMO and the DNA damage response

Bhachoo,

Garvin

2024

Biochemical Society Transactions

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“…Hence, this study demonstrated that MRE11 SUMOylation, in tandem with UB, is dynamically controlled by PIAS1 and SENP3 to facilitate DNA end excision and maintain genomic stability. 67 However, in contrast to studies of MRE11 phosphorylation, further in‐depth studies into MRE11 UB and ubiquitin‐like modifications (UBLs) are urgently needed (Figure 4B ).…”

Section: The Mrn Complex In Hrmentioning

confidence: 99%

Double‐strand DNA break repair: molecular mechanisms and therapeutic targets

Tan,

Sun,

Zhao

et al. 2023

MedComm

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Double‐strand break (DSB), a significant DNA damage brought on by ionizing radiation, acts as an initiating signal in tumor radiotherapy, causing cancer cells death. The two primary pathways for DNA DSB repair in mammalian cells are nonhomologous end joining (NHEJ) and homologous recombination (HR), which cooperate and compete with one another to achieve effective repair. The DSB repair mechanism depends on numerous regulatory variables. DSB recognition and the recruitment of DNA repair components, for instance, depend on the MRE11–RAD50–NBS1 (MRN) complex and the Ku70/80 heterodimer/DNA–PKcs (DNA–PK) complex, whose control is crucial in determining the DSB repair pathway choice and efficiency of HR and NHEJ. In‐depth elucidation on the DSB repair pathway's molecular mechanisms has greatly facilitated for creation of repair proteins or pathways‐specific inhibitors to advance precise cancer therapy and boost the effectiveness of cancer radiotherapy. The architectures, roles, molecular processes, and inhibitors of significant target proteins in the DSB repair pathways are reviewed in this article. The strategy and application in cancer therapy are also discussed based on the advancement of inhibitors targeted DSB damage response and repair proteins.

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Insights on the biological functions and diverse regulation of RNA-binding protein 39 and their implication in human diseases

Eléouët

Zhou

et al. 2023

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Crosstalk between SUMOylation and ubiquitylation controls DNA end resection by maintaining MRE11 homeostasis on chromatin

Cited by 11 publications

References 63 publications

SUMO and the DNA damage response

SUMO and the DNA damage response

Double‐strand DNA break repair: molecular mechanisms and therapeutic targets

Insights on the biological functions and diverse regulation of RNA-binding protein 39 and their implication in human diseases

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