The DNA Translocase FANCM/MHF Promotes Replication Traverse of DNA Interstrand Crosslinks

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Nov 12

PMID 24207054

Citations 131

Authors

Jing Huang

Shuo Liu

Marina A Bellani

Arun Kalliat Thazhathveetil

Chen Ling

Johan P de Winter

Yinsheng Wang

Weidong Wang

Michael M Seidman

Affiliations

Soon will be listed here.

Abstract

The replicative machinery encounters many impediments, some of which can be overcome by lesion bypass or replication restart pathways, leaving repair for a later time. However, interstrand crosslinks (ICLs), which preclude DNA unwinding, are considered absolute blocks to replication. Current models suggest that fork collisions, either from one or both sides of an ICL, initiate repair processes required for resumption of replication. To test these proposals, we developed a single-molecule technique for visualizing encounters of replication forks with ICLs as they occur in living cells. Surprisingly, the most frequent patterns were consistent with replication traverse of an ICL, without lesion repair. The traverse frequency was strongly reduced by inactivation of the translocase and DNA binding activities of the FANCM/MHF complex. The results indicate that translocase-based mechanisms enable DNA synthesis to continue past ICLs and that these lesions are not always absolute blocks to replication.

Citing Articles

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