DNA nucleases bind monoubiquitinated ID2 complex

Stable Identifier
Reaction [binding]
Homo sapiens
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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
15572677 DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation

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

Mol Cell Biol 2004
20603015 Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2

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

Cell 2010
25500724 Structural insights into 5' flap DNA unwinding and incision by the human FAN1 dimer

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Cell 2010
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