Helq acts in parallel to Fancc to suppress replication-associated genome instability

Spencer W. Luebben, Tsuyoshi Kawabata, Monica K. Akre, Wai Long Lee, Charles S. Johnson, M. Gerard O'Sullivan, Naoko Shima

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


HELQ is a superfamily 2 DNA helicase found in archaea and metazoans. It has been implicated in processing stalled replication forks and in repairing DNA double-strand breaks and inter-strand crosslinks. Though previous studies have suggested the possibility that HELQ is involved in the Fanconi anemia (FA) pathway, a dominant mechanism for inter-strand crosslink repair in vertebrates, this connection remains elusive. Here, we investigated this question in mice using the Helqgt and Fancc- strains. Compared with Fancc-/- mice lacking FANCC, a component of the FA core complex, Helqgt/gt mice exhibited a mild of form of FA-like phenotypes including hypogonadism and cellular sensitivity to the crosslinker mitomycin C. However, unlike Fancc-/- primary fibroblasts, Helqgt/gt cells had intact FANCD2 mono-ubiquitination and focus formation. Notably, for all traits examined, Helq was non-epistatic with Fancc, as Helqgt/gt;Fancc- /- double mutants displayed significantly worsened phenotypes than either single mutant. Importantly, this was most noticeable for the suppression of spontaneous chromosome instability such as micronuclei and 53BP1 nuclear bodies, known consequences of persistently stalled replication forks. These findings suggest that mammalian HELQ contributes to genome stability in unchallenged conditions through a mechanism distinct from the function of FANCC.

Original languageEnglish (US)
Pages (from-to)10283-10297
Number of pages15
JournalNucleic acids research
Issue number22
StatePublished - Dec 2013

Bibliographical note

Funding Information:
A postdoctoral fellowship from the Japan Society for the promotion of Science (to T.K.); March of Dimes [5-FY07-110 to N.S.]; and National Institutes of Health (NIH) [R01CA148806 to N.S.]. Funding for open access charge: University of Minnesota.


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