The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-Mediated Rad51 Loading onto ssDNA during Homologous Recombination in Human Cells

Molecular Cell
Ting-Hsiang HuangJessica K Tyler

Abstract

The access-repair-restore model for the role of chromatin in DNA repair infers that chromatin is a mere obstacle to DNA repair. However, here we show that blocking chromatin assembly, via knockdown of the histone chaperones ASF1 or CAF-1 or a mutation that prevents ASF1A binding to histones, hinders Rad51 loading onto ssDNA during homologous recombination. This is a consequence of reduced recruitment of the Rad51 loader MMS22L-TONSL to ssDNA, resulting in persistent RPA foci, extensive DNA end resection, persistent activation of the ATR-Chk1 pathway, and cell cycle arrest. In agreement, histones occupy ssDNA during DNA repair in yeast. We also uncovered DNA-PKcs-dependent DNA damage-induced ASF1A phosphorylation, which enhances chromatin assembly, promoting MMS22L-TONSL recruitment and, hence, Rad51 loading. We propose that transient assembly of newly synthesized histones onto ssDNA serves to recruit MMS22L-TONSL to efficiently form the Rad51 nucleofilament for strand invasion, suggesting an active role of chromatin assembly in homologous recombination.

Citations

Jun 10, 2018·Plant, Cell & Environment·Krzysztof BrzezinkaIsabel Bäurle
Jun 22, 2019·Genetics·Ujani ChakrabortyEric Alani
Nov 22, 2018·Disease Models & Mechanisms·Carmen Hurtado Del PozoNuria Montserrat
Feb 26, 2019·Nature Cell Biology·Kyosuke NakamuraAnja Groth
Jul 10, 2019·International Journal of Molecular Sciences·Yanjun ZhangSheng-You Huang
Aug 14, 2020·Cells·Radoslav AleksandrovAnastas Gospodinov
Apr 12, 2019·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Zoe E GillespieJuan Ausió
Jul 16, 2019·Cellular and Molecular Life Sciences : CMLS·Sandra Segura-Bayona, Travis H Stracker
Apr 25, 2019·Essays in Biochemistry·Alonso J PardalAndrew J Bowman
Sep 5, 2020·Journal of Hematology & Oncology·Win TopatanaXiujun Cai
Nov 11, 2020·Cells·Juliette FerrandSophie E Polo
Jul 22, 2020·Seminars in Cell & Developmental Biology·Juliette FerrandSophie E Polo
Feb 13, 2021·Personalized Medicine·Zhenxing FengTieshuan Tian
Feb 12, 2021·Current Opinion in Plant Biology·Vicky OberkoflerIsabel Bäurle
Feb 2, 2019·Molecular Cell·Dali ZongAndré Nussenzweig
Apr 16, 2021·Molecular Cell·Kenta ShinodaAndré Nussenzweig
Dec 29, 2020·The Plant Journal : for Cell and Molecular Biology·Karolína KolářováMartina Dvořáčková
Aug 1, 2019·Genetics·Ujani ChakrabortyEric Alani
May 4, 2021·FEBS Open Bio·Katiuska González-ArzolaMiguel A De la Rosa
Jun 15, 2021·Frontiers in Molecular Biosciences·Yiqiang LiuWeizhong Tang
Aug 23, 2021·DNA Repair·Chitra MohanJessica Tyler

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