Human Rad52 Promotes XPG-Mediated R-loop Processing to Initiate Transcription-Associated Homologous Recombination Repair (Cell 2018, 175:558–570)

報告日期: 2019/04/30
報告時間: 16:00/16:50
報告學生: 洪旭錦(以英文報告)
講評老師: 廖泓鈞

Human Rad52 Promotes XPG-Mediated R-loop Processing to Initiate Transcription-Associated Homologous Recombination

Yasuhara et al., 2018, Cell 175, 558–570

Speaker: Hsu-Chin Hung (洪旭錦)                      Time: 16:00 – 16:50 PM, April 30, 2019

Commentator: Hung-juin Liaw, PhD.                  Place: Room 602


DNA double-strand break (DSB) repair is crucial for the maintenance of genomic stability. Non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are two major mechanisms for DSB repair. Keeping genome without mutation is important to avoid diseases, such as cancers. Transcribed RNAs and DNA formed R-loop (a DNA-RNA hybrid and the non-template single-stranded DNAs) has been shown to facilitate DNA repair in S/G2 phase. Previous studies showed that the transcribed RNAs of R-loop near DSB site in transcriptionally active regions served as a template to initiate repair, resulting in pausing transcription process and contributed to genome maintenance. In addition, Rad52, a repair protein for HRR could promote DNA repair for genome maintenance. However, the molecular mechanisms of how Rad52 functions in transcription associated DSB repair remains unclear. In this study, the authors demonstrated that Rad52 was first recruited to the R-loop regions near the DSB sites while DSB occurred. They further found that except RNase H1, XPG was also involved in R-loop processing and subsequently initiated transcription-associated homologous recombination repair (TA-HRR). Additionally, they identified other DSB repair factors of HRR, including BRCA1, CtIP and ATM were also involved in the initiation of TA-HRR. On the contrary, the repair pathway switched to NHEJ resulted in increasing genomic aberrations suggested that TA-HRR mechanism was important for genome stability. In conclusion, RAD52 is important for initiation of TA-HRR mechanism and prevents genome alterations in transcriptionally active regions. Moreover, dysfunction of TA-HRR mechanism may contribute to the oncogenesis.


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