PMID- 33258468
OWN - NLM
STAT- MEDLINE
DCOM- 20210921
LR  - 20211203
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 29
IP  - 24
DP  - 2021 Feb 25
TI  - Double strand breaks (DSBs) as indicators of genomic instability in 
      PATRR-mediated translocations.
PG  - 3872-3881
LID - 10.1093/hmg/ddaa251 [doi]
AB  - Genomic instability contributes to a variety of potentially damaging conditions, 
      including DNA-based rearrangements. Breakage in the form of double strand breaks 
      (DSBs) increases the likelihood of DNA damage, mutations and translocations. 
      Certain human DNA regions are known to be involved in recurrent translocations, 
      such as the palindrome-mediated rearrangements that have been identified at the 
      breakpoints of several recurrent constitutional translocations: 
      t(11;22)(q23;q11), t(17;22)(q11;q11) and t(8;22) (q24;q11). These breakpoints 
      occur at the center of palindromic AT-rich repeats (PATRRs), which suggests that 
      the structure of the DNA may play a contributory role, potentially through the 
      formation of secondary cruciform structures. The current study analyzed the DSB 
      propensity of these PATRR regions in both lymphoblastoid (mitotic) and 
      spermatogenic cells (meiotic). Initial results found an increased association of 
      sister chromatid exchanges (SCEs) at PATRR regions in experiments that used SCEs 
      to assay DSBs, combining SCE staining with fluorescence in situ hybridization 
      (FISH). Additional experiments used chromatin immunoprecipitation (ChIP) with 
      antibodies for either markers of DSBs or proteins involved in DSB repair along 
      with quantitative polymerase chain reaction to quantify the frequency of DSBs 
      occurring at PATRR regions. The results indicate an increased rate of DSBs at 
      PATRR regions. Additional ChIP experiments with the cruciform binding 2D3 
      antibody indicate an increased rate of cruciform structures at PATRR regions in 
      both mitotic and meiotic samples. Overall, these experiments demonstrate an 
      elevated rate of DSBs at PATRR regions, an indication that the structure of PATRR 
      containing DNA may lead to increased breakage in multiple cellular environments.
CI  - (c) The Author(s) 2020. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Correll-Tash, Sarah
AU  - Correll-Tash S
AD  - Division of Human Genetics, The Children's Hospital of Philadelphia, 
      Philadelphia, PA 19104, USA.
FAU - Lilley, Brenna
AU  - Lilley B
AD  - Division of Human Genetics, The Children's Hospital of Philadelphia, 
      Philadelphia, PA 19104, USA.
FAU - Salmons Iv, Harold
AU  - Salmons Iv H
AD  - Division of Human Genetics, The Children's Hospital of Philadelphia, 
      Philadelphia, PA 19104, USA.
FAU - Mlynarski, Elisabeth
AU  - Mlynarski E
AD  - Division of Human Genetics, The Children's Hospital of Philadelphia, 
      Philadelphia, PA 19104, USA.
FAU - Franconi, Colleen P
AU  - Franconi CP
AD  - Division of Human Genetics, The Children's Hospital of Philadelphia, 
      Philadelphia, PA 19104, USA.
FAU - McNamara, Meghan
AU  - McNamara M
AD  - Division of Human Genetics, The Children's Hospital of Philadelphia, 
      Philadelphia, PA 19104, USA.
FAU - Woodbury, Carson
AU  - Woodbury C
AD  - Division of Human Genetics, The Children's Hospital of Philadelphia, 
      Philadelphia, PA 19104, USA.
FAU - Easley, Charles A
AU  - Easley CA
AD  - Department of Environmental Health Sciences, College of Public Health at the 
      University of Georgia, Athens, GA, 30602, USA.
FAU - Emanuel, Beverly S
AU  - Emanuel BS
AD  - Division of Human Genetics, The Children's Hospital of Philadelphia, 
      Philadelphia, PA 19104, USA.
AD  - Department of Pediatrics, Perelman School of Medicine of the University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
LA  - eng
GR  - K22 ES025418/ES/NIEHS NIH HHS/United States
GR  - R01 CA039926/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
SB  - IM
MH  - Aged
MH  - Chromosomes, Human/*genetics
MH  - *DNA Breaks, Double-Stranded
MH  - *Genomic Instability
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nucleic Acid Conformation
MH  - *Repetitive Sequences, Nucleic Acid
MH  - Spermatozoa/metabolism/*pathology
MH  - *Translocation, Genetic
PMC - PMC7906754
EDAT- 2020/12/02 06:00
MHDA- 2021/09/22 06:00
PMCR- 2021/12/01
CRDT- 2020/12/01 08:37
PHST- 2020/02/03 00:00 [received]
PHST- 2020/10/05 00:00 [revised]
PHST- 2020/11/25 00:00 [accepted]
PHST- 2020/12/02 06:00 [pubmed]
PHST- 2021/09/22 06:00 [medline]
PHST- 2020/12/01 08:37 [entrez]
PHST- 2021/12/01 00:00 [pmc-release]
AID - 6013611 [pii]
AID - ddaa251 [pii]
AID - 10.1093/hmg/ddaa251 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2021 Feb 25;29(24):3872-3881. doi: 10.1093/hmg/ddaa251.