TY - JOUR
T1 - Human RecQ Helicases in DNA Double-Strand Break Repair
AU - Lu, Huiming
AU - Davis, Anthony J.
N1 - Funding Information:
This research was supported by grants from the National Institutes of Health CA092584, CA162804, and GM04725 to AD and by an Initiative Seed Grant for Career Development from the Department of Radiation Oncology at UT Southwestern Medical Center to HL.
Publisher Copyright:
© Copyright © 2021 Lu and Davis.
PY - 2021/2/25
Y1 - 2021/2/25
N2 - RecQ DNA helicases are a conserved protein family found in bacteria, fungus, plants, and animals. These helicases play important roles in multiple cellular functions, including DNA replication, transcription, DNA repair, and telomere maintenance. Humans have five RecQ helicases: RECQL1, Bloom syndrome protein (BLM), Werner syndrome helicase (WRN), RECQL4, and RECQL5. Defects in BLM and WRN cause autosomal disorders: Bloom syndrome (BS) and Werner syndrome (WS), respectively. Mutations in RECQL4 are associated with three genetic disorders, Rothmund–Thomson syndrome (RTS), Baller–Gerold syndrome (BGS), and RAPADILINO syndrome. Although no genetic disorders have been reported due to loss of RECQL1 or RECQL5, dysfunction of either gene is associated with tumorigenesis. Multiple genetically independent pathways have evolved that mediate the repair of DNA double-strand break (DSB), and RecQ helicases play pivotal roles in each of them. The importance of DSB repair is supported by the observations that defective DSB repair can cause chromosomal aberrations, genomic instability, senescence, or cell death, which ultimately can lead to premature aging, neurodegeneration, or tumorigenesis. In this review, we will introduce the human RecQ helicase family, describe in detail their roles in DSB repair, and provide relevance between the dysfunction of RecQ helicases and human diseases.
AB - RecQ DNA helicases are a conserved protein family found in bacteria, fungus, plants, and animals. These helicases play important roles in multiple cellular functions, including DNA replication, transcription, DNA repair, and telomere maintenance. Humans have five RecQ helicases: RECQL1, Bloom syndrome protein (BLM), Werner syndrome helicase (WRN), RECQL4, and RECQL5. Defects in BLM and WRN cause autosomal disorders: Bloom syndrome (BS) and Werner syndrome (WS), respectively. Mutations in RECQL4 are associated with three genetic disorders, Rothmund–Thomson syndrome (RTS), Baller–Gerold syndrome (BGS), and RAPADILINO syndrome. Although no genetic disorders have been reported due to loss of RECQL1 or RECQL5, dysfunction of either gene is associated with tumorigenesis. Multiple genetically independent pathways have evolved that mediate the repair of DNA double-strand break (DSB), and RecQ helicases play pivotal roles in each of them. The importance of DSB repair is supported by the observations that defective DSB repair can cause chromosomal aberrations, genomic instability, senescence, or cell death, which ultimately can lead to premature aging, neurodegeneration, or tumorigenesis. In this review, we will introduce the human RecQ helicase family, describe in detail their roles in DSB repair, and provide relevance between the dysfunction of RecQ helicases and human diseases.
KW - BLM
KW - DNA double-strand break repair
KW - RECQL1
KW - RECQL4
KW - RECQL5
KW - RecQ helicase
KW - WRN
KW - genome stability
UR - http://www.scopus.com/inward/record.url?scp=85102451425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102451425&partnerID=8YFLogxK
U2 - 10.3389/fcell.2021.640755
DO - 10.3389/fcell.2021.640755
M3 - Review article
C2 - 33718381
AN - SCOPUS:85102451425
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
SN - 2296-634X
M1 - 640755
ER -