Transcription coupled DNA repair protein UVSSA binds to DNA and RNA: Mapping of nucleic acid interaction sites on human UVSSA

Mistry, Hiral; Gupta, Gagan D.

doi:10.1016/j.abb.2023.109515

Cited by 4 publications

(2 citation statements)

References 44 publications

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“…When elongating PolII is blocked by TBLs, CSB and CRL4 CSA are sequentially recruited. Then UVSSA and STK19 are recruited and bind to DNA (24,63), while RPB1-K1268 is ubiquitinated by CRL4 CSA with the help of ELOF1 and UVSSA (20). STK19, ELOF1 and RPB1-K1268ub can aid the mono-ubiquitination of UVSSA at K414 by CRL4 CSA (16,19).…”

Section: Discussionmentioning

confidence: 99%

STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading

Tan,

Gao,

Huang

et al. 2024

Preprint

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Transcription-coupled repair (TCR) is the major pathway to remove transcription-blocking lesions. Although discovered for nearly 40 years, the mechanism and critical players of mammalian TCR remain unclear. STK19 is a factor affecting cell survival and recovery of RNA synthesis in response to DNA damage, however, whether it is a necessary component for TCR is unknown. Here we demonstrated that STK19 is essential for human TCR. Mechanistically, STK19 is recruited to damage sites through direct interaction with CSA. It can also interact with RNA polymerase IIin vitro. Once recruited, STK19 plays an important role in UVSSA ubiquitination which is needed for TCR. STK19 also promotes TCR independent of UVSSA ubiquitination by stimulating TFIIH recruitment through its direct interaction with TFIIH. In summary, our results suggest that STK19 is a key factor of human TCR that links CSA, UVSSA ubiquitination and TFIIH loading, shedding light on the molecular mechanisms of TCR.

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Section: Discussionmentioning

confidence: 99%

STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading

Tan,

Gao,

Huang

et al. 2024

Preprint

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“…To disrupt TCR while maintaining the recruitment and deubiquitinase activity of UVSSA-USP7, we expressed the UVSSA-V411A mutant in UVSSA-KO cells, since the V411 residue is essential for its interaction with the p62 subunit of TFIIH but not 14 required for UVSSA-USP7 interaction (Fig. 5a,b) 15,44,47 . Damage-seq showed that expression of UVSSA-WT, but not UVSSA-V411A, could efficiently rescue TCR (Fig.…”

Section: Usp7 Is Involved In Tcr But Cannot Abolish Repair-independen...mentioning

confidence: 99%

Coordination of transcription-coupled repair and repair-independent release of stalled RNA polymerase II in response to transcription-blocking lesions

Zhu,

Zhang,

Gao

et al. 2024

Preprint

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Transcription-blocking lesions (TBLs) stall elongating RNA polymerase II (PolII), which then initiates transcription-coupled repair (TCR) to remove TBLs and allow transcription recovery. In the absence of TCR, eviction of lesion-stalled PolII is required for alternative pathways to address the damage, but the mechanism is unclear. This study, utilizing Protein-Associated DNA Damage Sequencing (PADD-seq), reveals that the p97-proteasome pathway can evict lesion-stalled PolII independently of repair. Both TCR and repair-independent eviction require CSA and ubiquitination. However, p97 is dispensable for TCR and PolII eviction in TCR-proficient cells, highlighting repair’s prioritization over repair-independent eviction. Moreover, ubiquitination of RPB1-K1268 is important for both pathways, with USP7’s deubiquitinase activity promoting TCR without abolishing repair-independent PolII release. In summary, this study elucidates the fate of lesion-stalled PolII, and may shed light on the molecular basis of genetic diseases caused by the defects of TCR genes.

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Structural characterization of transcription-coupled repair protein UVSSA and its interaction with TFIIH protein

Mistry

Kumari

Aswal

et al. 2023

International Journal of Biological Macromolecules

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Transcription coupled DNA repair protein UVSSA binds to DNA and RNA: Mapping of nucleic acid interaction sites on human UVSSA

Cited by 4 publications

References 44 publications

STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading

STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading

Coordination of transcription-coupled repair and repair-independent release of stalled RNA polymerase II in response to transcription-blocking lesions

Structural characterization of transcription-coupled repair protein UVSSA and its interaction with TFIIH protein

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