Page 88 - ebook

[A. Biochemistry/Molecular Biology] A-44

The chromatin remodeler RSF1 coordinates epigenetic marks

for transcriptional repression and DSB repair

#
#
Sunwoo Min¹,² *, Ho-Soo Lee¹,² , Jae-Hoon Ji²,³, Yungyeong Heo⁴, Yonghyeon Kim⁴, Hyeseong Cho¹,²*
¹Department of Biochemistry, Ajou University School of Medicine, Suwon 16499, Korea, ²Genomic Instability

Research Center, Ajou University School of Medicine, Suwon 16499, Korea, ³Department of Biochemistry and

Structural Biology, The University of Texas Health San Antonio, TX 78229-3000, USA, ⁴Department of Biomedical
Sciences, the Graduate School of Ajou University, Suwon 16499, Korea

DNA lesions impact on local transcription and the damage-induced transcriptional repression facilitates efficient

DNA repair. However, how chromatin dynamics cooperates with these two events remained largely unknown. We
here show that histone H2A acetylation at K118 is enriched in transcriptionally active regions. Under DNA damage,

the RSF1 chromatin remodeling factor recruits HDAC1 to DSB sites. The RSF1-HDAC1 complex induces the
deacetylation of H2A(X)-K118 and its deacetylation is indispensable for the ubiquitination of histone H2A at K119.

Accordingly, the acetylation mimetic H2AK118Q suppressed the H2A-K119ub level, perturbing the transcriptional
repression at DNA lesions. Intriguingly, deacetylation of H2AX at K118 also licenses the propagation of H2AX and

recruitment of MDC1. Consequently, the H2AX-K118Q limits DNA repair. Together, the RSF1-HDAC1 complex
controls the traffic of the DNA damage response and transcription simultaneously in transcriptionally active

chromatins. The interplay between chromatin remodelers and histone modifiers highlights the importance of
chromatin versatility in the maintenance of genome integrity.