DNA nucleases bind monoubiquitinated ID2 complex

Stable Identifier
R-HSA-6785732
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Several DNA nucleases bind to interstrand crosslinks (ICL-DNA) and participate in ICL "unhooking". The ubiquitin-binding zinc finger (UBZ) domain of the DNA nuclease FAN1 binds to monoubiquitinated FANCD2, enabling the recruitment of FAN1 to the ICL-DNA repair site (Liu et al. 2010, MacKay et al. 2010, Smogorzewska et al. 2010, Kratz et al. 2010). Once recruited to ICL-DNA, FAN1 forms head-to-tail homodimers. Homodimerization is important for the endonucleolytic activity of FAN1 (Zhao et al. 2014). SLX4 (FANCP) serves as a docking platform for recruitment of SLX1A, MUS81 and EME1 or EME2, resulting in formation of the SLX1A:SLX4:MUS81:EME1 (or SLX1A:SLX4:MUS81:EME2) endonucleolytic complex (Fekairi et al. 2009, Wyatt et al. 2013). SLX4 can also bind the endonucleolytic complex composed of ERCC1 and ERCC4 (XPF) (Fekairi et al. 2009). SLX4 is recruited to ICL-DNA through interaction of the UBZ domain of SLX4 with monoubiquitinated FANCD2 (Yamamoto et al. 2011). Targeted deletion of the UBZ domain of SLX4 confers sensitivity to ICL-inducing agents, but the UBZ domain seems to be dispensable for the role of SLX4 in homologous recombination repair (Yamamoto et al. 2011).

DNA exonucleases DCLRE1A (SNM1A) and DCLRE1B (SNM1B) likely function redundantly in ICL repair. Similar to FAN1, they are able to digest the DNA past the ICL, thereby unhooking one of the DNA strands (Wang et al. 2011, Sengerova et al. 2012). Monoubiquitination of the PCNA subunit of the stalled replicative polymerase complex by RAD18 may provide the docking site for DCLRE1A (or DCLRE1B) (Yang et al. 2010). In addition, PIAS1 may facilitate loading of DCLRE1A (or DCLRE1B) to ICL sites (Ishiai et al. 2004).

Literature References
PubMed ID Title Journal Year
20603015 Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2

MacKay, C, Déclais, AC, Lundin, C, Agostinho, A, Deans, AJ, Macartney, TJ, Hofmann, K, Gartner, A, West, SC, Helleday, T, Lilley, DM, Rouse, J

Cell 2010
15572677 DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation

Ishiai, M, Kimura, M, Namikoshi, K, Yamazoe, M, Yamamoto, K, Arakawa, H, Agematsu, K, Matsushita, N, Takeda, S, Buerstedde, JM, Takata, M

Mol Cell Biol 2004
25500724 Structural insights into 5' flap DNA unwinding and incision by the human FAN1 dimer

Zhao, Q, Xue, X, Longerich, S, Sung, P, Xiong, Y

Nat Commun 2014
22692201 Characterization of the human SNM1A and SNM1B/Apollo DNA repair exonucleases

Sengerová, B, Allerston, CK, Abu, M, Lee, SY, Hartley, J, Kiakos, K, Schofield, CJ, Hartley, JA, Gileadi, O, McHugh, PJ

J. Biol. Chem. 2012
24076221 Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells

Wyatt, HD, Sarbajna, S, Matos, J, West, SC

Mol. Cell 2013
20603073 A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair

Smogorzewska, A, Desetty, R, Saito, TT, Schlabach, M, Lach, FP, Sowa, ME, Clark, AB, Kunkel, TA, Harper, JW, Colaiácovo, MP, Elledge, SJ

Mol. Cell 2010
21464321 Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway

Yamamoto, KN, Kobayashi, S, Tsuda, M, Kurumizaka, H, Takata, M, Kono, K, Jiricny, J, Takeda, S, Hirota, K

Proc. Natl. Acad. Sci. U.S.A. 2011
20385554 RAD18-dependent recruitment of SNM1A to DNA repair complexes by a ubiquitin-binding zinc finger

Yang, K, Moldovan, GL, D'Andrea, AD

J. Biol. Chem. 2010
19596236 Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases

Fekairi, S, Scaglione, S, Chahwan, C, Taylor, ER, Tissier, A, Coulon, S, Dong, MQ, Ruse, C, Yates, JR, Russell, P, Fuchs, RP, McGowan, CH, Gaillard, PH

Cell 2009
20671156 FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair

Liu, T, Ghosal, G, Yuan, J, Chen, J, Huang, J

Science 2010
20603016 Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents

Kratz, K, Schöpf, B, Kaden, S, Sendoel, A, Eberhard, R, Lademann, C, Cannavó, E, Sartori, AA, Hengartner, MO, Jiricny, J

Cell 2010
Participants
Participant Of
This event is regulated
Negatively by
Orthologous Events
Authored
Reviewed
Created