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-Structure paper
タイトル | Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination. |
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ジャーナル・号・ページ | EMBO J, Vol. 42, Issue 3, Page e111898, Year 2023 |
掲載日 | 2023年2月1日 |
![]() | Kimon Lemonidis / Martin L Rennie / Connor Arkinson / Viduth K Chaugule / Mairi Clarke / James Streetley / Helen Walden / ![]() |
PubMed 要旨 | Di-monoubiquitination of the FANCI-FANCD2 (ID2) complex is a central and crucial step for the repair of DNA interstrand crosslinks via the Fanconi anaemia pathway. While FANCD2 ubiquitination ...Di-monoubiquitination of the FANCI-FANCD2 (ID2) complex is a central and crucial step for the repair of DNA interstrand crosslinks via the Fanconi anaemia pathway. While FANCD2 ubiquitination precedes FANCI ubiquitination, FANCD2 is also deubiquitinated at a faster rate than FANCI, which can result in a FANCI-ubiquitinated ID2 complex (I D2). Here, we present a 4.1 Å cryo-EM structure of I D2 complex bound to double-stranded DNA. We show that this complex, like ID2 and I D2 , is also in the closed ID2 conformation and clamps on DNA. The target lysine of FANCD2 (K561) becomes fully exposed in the I D2-DNA structure and is thus primed for ubiquitination. Similarly, FANCI's target lysine (K523) is also primed for ubiquitination in the ID2 -DNA complex. The I D2-DNA complex exhibits deubiquitination resistance, conferred by the presence of DNA and FANCD2. ID2 -DNA, on the other hand, can be efficiently deubiquitinated by USP1-UAF1, unless further ubiquitination on FANCI occurs. Therefore, FANCI ubiquitination effectively maintains FANCD2 ubiquitination in two ways: it prevents excessive FANCD2 deubiquitination within an I D2 -DNA complex, and it enables re-ubiquitination of FANCD2 within a transient, closed-on-DNA, I D2 complex. |
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手法 | EM (単粒子) |
解像度 | 4.14 Å |
構造データ | EMDB-14694, PDB-7zf1: |
由来 |
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![]() | DNA BINDING PROTEIN / Fanconi anemia / DNA repair / ubiquitination / ID2 complex |