윤한솔 (아주대학교 의과대학) | 한빛사논문 > 한빛사

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윤한솔Hansol Yun

아주대학교 의과대학

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Nucleic Acids Res., Feb 27 2024, gkae156 | https://doi.org/10.1093/nar/gkae156 LC3B drives transcription-associated homologous recombination via direct interaction with R-loops

Junghyun Yoon ^1,2,†, Yiseul Hwang ^1,2,†, Hansol Yun ^1,2,†, Jee Min Chung ^1,2, So yeon Kim ^1,2, Gyeongmin Kim^1,2, Yeji Lee ^1,2, Byoung Dae Lee ³ and Ho Chul Kang ^1,2,4,*

¹Department of Physiology, Ajou University School of Medicine, Suwon, Gyeonggi 16499, Republic of Korea

²Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Gyeonggi 16499, Republic of Korea

³Department of Neuroscience, Kyung Hee University, Seoul 02447; Department of Physiology, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea

⁴Genomic Instability Research Center, Ajou University School of Medicine, Suwon, Gyeonggi 16499, Republic of Korea

^*To whom correspondence should be addressed.: Ho Chul Kang

^†The first three authors should be regarded as Joint First Authors.

Abstract

Exploring the connection between ubiquitin-like modifiers (ULMs) and the DNA damage response (DDR), we employed several advanced DNA damage and repair assay techniques and identified a crucial role for LC3B. Notably, its RNA recognition motif (RRM) plays a pivotal role in the context of transcription-associated homologous recombination (HR) repair (TA-HRR), a particular subset of HRR pathways. Surprisingly, independent of autophagy flux, LC3B interacts directly with R-loops at DNA lesions within transcriptionally active sites via its RRM, promoting TA-HRR. Using native RNA immunoprecipitation (nRIP) coupled with high-throughput sequencing (nRIP-seq), we discovered that LC3B also directly interacts with the 3'UTR AU-rich elements (AREs) of BRCA1 via its RRM, influencing its stability. This suggests that LC3B regulates TA-HRR both proximal to and distal from DNA lesions. Data from our LC3B depletion experiments showed that LC3B knockdown disrupts end-resection for TA-HRR, redirecting it towards the non-homologous end joining (NHEJ) pathway and leading to chromosomal instability, as evidenced by alterations in sister chromatid exchange (SCE) and interchromosomal fusion (ICF). Thus, our findings unveil autophagy-independent functions of LC3B in DNA damage and repair pathways, highlighting its importance. This could reshape our understanding of TA-HRR and the interaction between autophagy and DDR.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-29)
연구진국내 연구진
분야 생명과학 > 신경생물학

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