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Review
. 2020 May 21;11(5):578.
doi: 10.3390/genes11050578.

Genome Maintenance by DNA Helicase B

Lindsey Hazeslip  1 , Maroof Khan Zafar  1 , Muhammad Zain Chauhan  1 , Alicia K Byrd  1   2
Affiliations
Review

Genome Maintenance by DNA Helicase B

Lindsey Hazeslip et al. Genes (Basel). .

Abstract

DNA Helicase B (HELB) is a conserved helicase in higher eukaryotes with roles in the initiation of DNA replication and in the DNA damage and replication stress responses. HELB is a predominately nuclear protein in G1 phase where it is involved in initiation of DNA replication through interactions with DNA topoisomerase 2-binding protein 1 (TOPBP1), cell division control protein 45 (CDC45), and DNA polymerase α-primase. HELB also inhibits homologous recombination by reducing long-range end resection. After phosphorylation by cyclin-dependent kinase 2 (CDK2) at the G1 to S transition, HELB is predominately localized to the cytosol. However, this cytosolic localization in S phase is not exclusive. HELB has been reported to localize to chromatin in response to replication stress and to localize to the common fragile sites 16D (FRA16D) and 3B (FRA3B) and the rare fragile site XA (FRAXA) in S phase. In addition, HELB is phosphorylated in response to ionizing radiation and has been shown to localize to chromatin in response to various types of DNA damage, suggesting it has a role in the DNA damage response.

Keywords: DNA damage; DNA helicase; DNA repair; DNA replication; genomic stability.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
HELB domain structure. HELB has a N-terminal domain, a helicase domain that binds DNA [6], hydrolyzes ATP [2], and interacts with RPA [7], and a subcellular localization domain (SLD) [7]. The SLD is phosphorylated by CDK2 at the G1 to S transition [7] and the helicase domain is phosphorylated in response to ionizing radiation [12]. Note that the boundary between the N-terminal domain and helicase domain here is different than originally reported [2] due to the discovery of the Q-motif N-terminal to the first helicase motif identified at the time of the original report [9,13].
Figure 2
Figure 2
Functions of HELB. Roles for HELB in loading the pre-initiation complex (A), inhibition of end resection (B), recovery from replication stress (C), and in replication of fragile sties (D) have been proposed [2,6,10,15].
See this image and copyright information in PMC

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