Chaperoning of the histone octamer by the acidic domain of DNA repair factor APLF

Corbeski, Ivan; Guo, Xiaohu; Eckhardt, Bruna V.; Fasci, Domenico; Wiegant, Wouter W.; Graewert, Melissa A.; Vreeken, Kees; Wienk, Hans; Svergun, Dmitri I.; Heck, Albert J. R.; Attikum, Haico van; Boelens, Rolf; Sixma, Titia K.; Mattiroli, Francesca; Ingen, Hugo van

doi:10.1126/sciadv.abo0517

Cited by 21 publications

(12 citation statements)

References 69 publications

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“…Experimental structural biology would be required to confirm these models. The ability of a peptide to act as a chaperone for an intact histone octamer has been observed before for the APLF peptide ( 28, 30 ). The MIER1:octamer complex would appear to allow initial binding of DNA to the H3:H4 dyad position.…”

Section: Discussionsupporting

confidence: 53%

An unexpected histone chaperone function for the MIER1 histone deacetylase complex

Wang

Fairall

Pham

et al. 2022

Preprint

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Histone deacetylases 1 and 2 (HDAC1/2) serve as the catalytic subunit of six distinct families of nuclear complexes. These complexes repress gene transcription through removing acetyl groups from lysine residues in histone tails. In addition to the deacetylase subunit, these complexes typically contain transcription factor and/or chromatin binding activities. The MIER:HDAC complex has hitherto been poorly characterized. Here we show that MIER1 unexpectedly co-purifies with an H2A:H2B histone dimer. We show that MIER1 is also able to bind a complete histone octamer. Intriguingly, we found that a larger MIER1:HDAC1:BAHD1:C1QBP complex additionally co-purifies with an intact nucleosome on which H3K27 is either di- or tri-methylated. Together this suggests that the MIER1 complex acts downstream of PRC2 to expand regions of repressed chromatin and to deposit histone octamer onto nucleosome-depleted regions of DNA.

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Section: Discussionsupporting

confidence: 53%

An unexpected histone chaperone function for the MIER1 histone deacetylase complex

Wang

Fairall

Pham

et al. 2022

Preprint

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“…While H2A H2B may be released directly to the assembling nucleosome, it could also be released to another H2A-H2B chaperone. Candidate chaperones include Nap1, FACT, or APLF (Chen et al 2016; Liu et al 2020; Corbeski et al 2022).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of RanGTP priming H2A-H2B release from Kap114 in an atypical RanGTP•Kap114•H2A-H2B complex

Jiou

Shaffer²,

Bernardes

et al. 2022

Preprint

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Previously we showed that the nuclear import receptor Importin-9 wraps around the H2A-H2B core to chaperone and transport it from the cytoplasm to the nucleus (Padavannil et al. 2019). However, unlike most nuclear import systems where RanGTP dissociates cargoes from their importins, RanGTP binds stably to the Importin-9•H2A-H2B complex and formation of RanGTP•Importin-9•H2A-H2B facilitates H2A-H2B release to the assembling nucleosome (Padavannil et al. 2019). Here we show cryo-EM structures of Importin-9•RanGTP and of its yeast homolog Kap114, including Kap114•RanGTP, Kap114•H2A-H2B, and RanGTP•Kap114•H2A-H2B. In combination with hydrogen-deuterium exchange analysis of Importin-9 complexes and nucleosome assembly assays, we explain how the conserved Kap114/Importin-9 importins bind H2A-H2B and RanGTP simultaneously and how the GTPase primes histone transfer to the nucleosome. We show that RanGTP binds to the N-terminal repeats of Kap114/Importin-9 as in Kap114/Importin-9•RanGTP, and H2A-H2B binds via its acidic patch to the Kap114/Importin-9 C-terminal repeats as in Kap114/Importin-9•H2A-H2B. RanGTP-binding in RanGTP•Kap114•H2A-H2B changes Kap114/Importin-9 conformation such that it no longer contacts the surface of H2A-H2B proximal to the H2A docking domain that drives nucleosome assembly, positioning it for transfer to the assembling nucleosome. The reduced affinity of RanGTP for Kap114/Importin-9 when H2A-H2B is bound may ensure release of H2A-H2B only at chromatin.

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“…This region has been reported to be involved in the binding to histones. 33 Importantly, our data using APLF showed that the lack of the acidic domain abolished the formation of stable synaptic events (Figure 2D). This observation contrasts with the results obtained for wild-type APLF (Figure 1E).…”

Section: The Aplf C-terminal Acidic Domain Is Critical For Dna End Br...mentioning

confidence: 76%

“…18,30 APLF also interacts with poly(ADP-ribose) (PAR) via two PAR-binding zinc finger (PBZ) domains 31,32 and binds histones through its C-terminal disordered acidic region. 33,34 APLF facilitates NHEJ, at least in part, by promoting the formation and/or the stability of complexes between Ku and X4-LIG4 on the DNA, which are required for an efficient ligation. 25 Besides protein factors, accumulating evidence shows that some long non-coding RNAs (lncRNAs) regulate DNA damage response pathways.…”

Section: Introductionmentioning

confidence: 99%

APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining

Bragança¹,

Aicart-Ramos²,

Arribas-Bosacoma³

et al. 2023

Cell Reports

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Chaperoning of the histone octamer by the acidic domain of DNA repair factor APLF

Cited by 21 publications

References 69 publications

An unexpected histone chaperone function for the MIER1 histone deacetylase complex

An unexpected histone chaperone function for the MIER1 histone deacetylase complex

Mechanism of RanGTP priming H2A-H2B release from Kap114 in an atypical RanGTP•Kap114•H2A-H2B complex

APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining

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