Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword?
DNA damage repair response is an important biological process involved in maintaining the fidelity of the genome in eukaryotes and prokaryotes. Several proteins that play a key role in this process have been identified. Alterations in these key proteins have been linked to different diseases includi...
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doaj-dcaf2228434d4a1b98ac510397ddc0d22021-03-12T06:52:20ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-03-011210.3389/fgene.2021.634789634789Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword?Ekjot KaurRitu AgrawalSagar SenguptaDNA damage repair response is an important biological process involved in maintaining the fidelity of the genome in eukaryotes and prokaryotes. Several proteins that play a key role in this process have been identified. Alterations in these key proteins have been linked to different diseases including cancer. BLM is a 3′−5′ ATP-dependent RecQ DNA helicase that is one of the most essential genome stabilizers involved in the regulation of DNA replication, recombination, and both homologous and non-homologous pathways of double-strand break repair. BLM structure and functions are known to be conserved across many species like yeast, Drosophila, mouse, and human. Genetic mutations in the BLM gene cause a rare, autosomal recessive disorder, Bloom syndrome (BS). BS is a monogenic disease characterized by genomic instability, premature aging, predisposition to cancer, immunodeficiency, and pulmonary diseases. Hence, these characteristics point toward BLM being a tumor suppressor. However, in addition to mutations, BLM gene undergoes various types of alterations including increase in the copy number, transcript, and protein levels in multiple types of cancers. These results, along with the fact that the lack of wild-type BLM in these cancers has been associated with increased sensitivity to chemotherapeutic drugs, indicate that BLM also has a pro-oncogenic function. While a plethora of studies have reported the effect of BLM gene mutations in various model organisms, there is a dearth in the studies undertaken to investigate the effect of its oncogenic alterations. We propose to rationalize and integrate the dual functions of BLM both as a tumor suppressor and maybe as a proto-oncogene, and enlist the plausible mechanisms of its deregulation in cancers.https://www.frontiersin.org/articles/10.3389/fgene.2021.634789/fullBLM helicasetumor suppressoroncogeneRecQ helicaseneoplastic transformation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ekjot Kaur Ritu Agrawal Sagar Sengupta |
spellingShingle |
Ekjot Kaur Ritu Agrawal Sagar Sengupta Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword? Frontiers in Genetics BLM helicase tumor suppressor oncogene RecQ helicase neoplastic transformation |
author_facet |
Ekjot Kaur Ritu Agrawal Sagar Sengupta |
author_sort |
Ekjot Kaur |
title |
Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword? |
title_short |
Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword? |
title_full |
Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword? |
title_fullStr |
Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword? |
title_full_unstemmed |
Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword? |
title_sort |
functions of blm helicase in cells: is it acting like a double-edged sword? |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2021-03-01 |
description |
DNA damage repair response is an important biological process involved in maintaining the fidelity of the genome in eukaryotes and prokaryotes. Several proteins that play a key role in this process have been identified. Alterations in these key proteins have been linked to different diseases including cancer. BLM is a 3′−5′ ATP-dependent RecQ DNA helicase that is one of the most essential genome stabilizers involved in the regulation of DNA replication, recombination, and both homologous and non-homologous pathways of double-strand break repair. BLM structure and functions are known to be conserved across many species like yeast, Drosophila, mouse, and human. Genetic mutations in the BLM gene cause a rare, autosomal recessive disorder, Bloom syndrome (BS). BS is a monogenic disease characterized by genomic instability, premature aging, predisposition to cancer, immunodeficiency, and pulmonary diseases. Hence, these characteristics point toward BLM being a tumor suppressor. However, in addition to mutations, BLM gene undergoes various types of alterations including increase in the copy number, transcript, and protein levels in multiple types of cancers. These results, along with the fact that the lack of wild-type BLM in these cancers has been associated with increased sensitivity to chemotherapeutic drugs, indicate that BLM also has a pro-oncogenic function. While a plethora of studies have reported the effect of BLM gene mutations in various model organisms, there is a dearth in the studies undertaken to investigate the effect of its oncogenic alterations. We propose to rationalize and integrate the dual functions of BLM both as a tumor suppressor and maybe as a proto-oncogene, and enlist the plausible mechanisms of its deregulation in cancers. |
topic |
BLM helicase tumor suppressor oncogene RecQ helicase neoplastic transformation |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2021.634789/full |
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