Structural Insights into the Functions of the FANCM-FAAP24 Complex in DNA Repair

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2013 Sep 5

PMID 24003026

Citations 11

Authors

Hui Yang

Tianlong Zhang

Ye Tao

Fang Wang

Liang Tong

Jianping Ding

Affiliations

Soon will be listed here.

Abstract

Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair.

Citing Articles

[Homozygous Variant of of the Fanconi Anemia Pathway Causes Premature Ovarian Insufficiency: Investigation of the Pathogenic Mechanism].

Wen X, Chai M, Zhang Q, Zou H, Zhang Z, Cao Y Sichuan Da Xue Xue Bao Yi Xue Ban. 2024; 55(3):559-565.

PMID: 38948269 PMC: 11211784. DOI: 10.12182/20240560207.

Regulation of Replication Stress in Alternative Lengthening of Telomeres by Fanconi Anaemia Protein.

Li D, Hou K, Zhang K, Jia S Genes (Basel). 2022; 13(2).

PMID: 35205225 PMC: 8872277. DOI: 10.3390/genes13020180.

Novel Bi-Allelic Variants of Cause Sertoli Cell-Only Syndrome and Non-Obstructive Azoospermia.

Zhang Y, Li P, Liu N, Jing T, Ji Z, Yang C Front Genet. 2022; 12:799886.

PMID: 34976027 PMC: 8714797. DOI: 10.3389/fgene.2021.799886.

Fanconi anemia pathway as a prospective target for cancer intervention.

Liu W, Palovcak A, Li F, Zafar A, Yuan F, Zhang Y Cell Biosci. 2020; 10:39.

PMID: 32190289 PMC: 7075017. DOI: 10.1186/s13578-020-00401-7.

ALTernative Functions for Human FANCM at Telomeres.

Domingues-Silva B, Silva B, Azzalin C Front Mol Biosci. 2019; 6:84.

PMID: 31552268 PMC: 6743340. DOI: 10.3389/fmolb.2019.00084.

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