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Article: Chromatin's Influence on Pre-Replication Complex Assembly and Function.

Ahmad, Hina / Chetlangia, Neha / Prasanth, Supriya G

2024 Volume 13, Issue 3

Abstract: In all eukaryotes, the initiation of DNA replication requires a stepwise assembly of factors onto the origins of DNA replication. This is pioneered by the Origin Recognition Complex, which recruits Cdc6. Together, they bring Cdt1, which shepherds MCM2-7 ... ...

Abstract	In all eukaryotes, the initiation of DNA replication requires a stepwise assembly of factors onto the origins of DNA replication. This is pioneered by the Origin Recognition Complex, which recruits Cdc6. Together, they bring Cdt1, which shepherds MCM2-7 to form the OCCM complex. Sequentially, a second Cdt1-bound hexamer of MCM2-7 is recruited by ORC-Cdc6 to form an MCM double hexamer, which forms a part of the pre-RC. Although the mechanism of ORC binding to DNA varies across eukaryotes, how ORC is recruited to replication origins in human cells remains an area of intense investigation. This review discusses how the chromatin environment influences pre-RC assembly, function, and, eventually, origin activity.
Language	English
Publishing date	2024-02-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology13030152
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Article ; Online: A BEN-domain protein and polycomb complex work coordinately to regulate transcription.

Kurniawan, Fredy / Prasanth, Supriya G

Transcription

2022 Volume 13, Issue 1-3, Page(s) 82–87

Abstract: Transcription regulation is an important mechanism that controls pluripotency and differentiation. Transcription factors dictate cell fate decisions by functioning cooperatively with chromatin regulators. We have recently demonstrated that BEND3 (BANP, ... ...

Abstract	Transcription regulation is an important mechanism that controls pluripotency and differentiation. Transcription factors dictate cell fate decisions by functioning cooperatively with chromatin regulators. We have recently demonstrated that BEND3 (BANP, E5R and Nac1 domain) protein regulates the expression of differentiation-associated genes by modulating the chromatin architecture at promoters. We highlight the collaboration of BEND3 with the polycomb repressive complex in coordinating transcription repression and propose a model highlighting the relevance of the BEND3-PRC2 axis in gene regulation and chromatin organization.
MeSH term(s)	Chromatin/genetics ; DNA, Ribosomal ; Drosophila Proteins/genetics ; Histones/genetics ; Histones/metabolism ; Methylation ; Polycomb Repressive Complex 2/genetics ; Polycomb-Group Proteins/genetics ; Polycomb-Group Proteins/metabolism
Chemical Substances	Chromatin ; DNA, Ribosomal ; Drosophila Proteins ; Histones ; Polycomb-Group Proteins ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
Language	English
Publishing date	2022-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2646974-1
ISSN	2154-1272 ; 2154-1264
ISSN (online)	2154-1272
ISSN	2154-1264
DOI	10.1080/21541264.2022.2105128
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Article ; Online: ORChestra coordinates the replication and repair music.

Liu, Dazhen / Sonalkar, Jay / Prasanth, Supriya G

BioEssays : news and reviews in molecular, cellular and developmental biology

2023 Volume 45, Issue 4, Page(s) e2200229

Abstract: Error-free genome duplication and accurate cell division are critical for cell survival. In all three domains of life, bacteria, archaea, and eukaryotes, initiator proteins bind replication origins in an ATP-dependent manner, play critical roles in ... ...

Abstract	Error-free genome duplication and accurate cell division are critical for cell survival. In all three domains of life, bacteria, archaea, and eukaryotes, initiator proteins bind replication origins in an ATP-dependent manner, play critical roles in replisome assembly, and coordinate cell-cycle regulation. We discuss how the eukaryotic initiator, Origin recognition complex (ORC), coordinates different events during the cell cycle. We propose that ORC is the maestro driving the orchestra to coordinately perform the musical pieces of replication, chromatin organization, and repair.
MeSH term(s)	DNA Replication ; Chromatin ; Music ; Cell Cycle/physiology ; Chromosomes ; Origin Recognition Complex/genetics ; Origin Recognition Complex/metabolism ; Replication Origin
Chemical Substances	Chromatin ; Origin Recognition Complex
Language	English
Publishing date	2023-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.202200229
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Article ; Online: Replication initiation: Implications in genome integrity.

Lin, Yo-Chuen / Prasanth, Supriya G

DNA repair

2021 Volume 103, Page(s) 103131

Abstract: In every cell cycle, billions of nucleotides need to be duplicated within hours, with extraordinary precision and accuracy. The molecular mechanism by which cells regulate the replication event is very complicated, and the entire process begins way ... ...

Abstract	In every cell cycle, billions of nucleotides need to be duplicated within hours, with extraordinary precision and accuracy. The molecular mechanism by which cells regulate the replication event is very complicated, and the entire process begins way before the onset of S phase. During the G1 phase of the cell cycle, cells prepare by assembling essential replication factors to establish the pre-replicative complex at origins, sites that dictate where replication would initiate during S phase. During S phase, the replication process is tightly coupled with the DNA repair system to ensure the fidelity of replication. Defects in replication and any error must be recognized by DNA damage response and checkpoint signaling pathways in order to halt the cell cycle before cells are allowed to divide. The coordination of these processes throughout the cell cycle is therefore critical to achieve genomic integrity and prevent diseases. In this review, we focus on the current understanding of how the replication initiation events are regulated to achieve genome stability.
MeSH term(s)	Animals ; Cell Cycle ; DNA Replication ; Eukaryota/genetics ; Genomic Instability ; Humans ; Replication Origin
Language	English
Publishing date	2021-05-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2071608-4
ISSN	1568-7856 ; 1568-7864
ISSN (online)	1568-7856
ISSN	1568-7864
DOI	10.1016/j.dnarep.2021.103131
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Article ; Online: ORChestra coordinates the replication and repair music

Liu, Dazhen / Sonalkar, Jay / Prasanth, Supriya G.

BioEssays. 2023 Apr., v. 45, no. 4 p.e2200229-

2023

Abstract: Error‐free genome duplication and accurate cell division are critical for cell survival. In all three domains of life, bacteria, archaea, and eukaryotes, initiator proteins bind replication origins in an ATP‐dependent manner, play critical roles in ... ...

Abstract	Error‐free genome duplication and accurate cell division are critical for cell survival. In all three domains of life, bacteria, archaea, and eukaryotes, initiator proteins bind replication origins in an ATP‐dependent manner, play critical roles in replisome assembly, and coordinate cell‐cycle regulation. We discuss how the eukaryotic initiator, Origin recognition complex (ORC), coordinates different events during the cell cycle. We propose that ORC is the maestro driving the orchestra to coordinately perform the musical pieces of replication, chromatin organization, and repair.
Keywords	Archaea ; cell division ; cell viability ; chromatin ; eukaryotic cells ; genome ; music
Language	English
Dates of publication	2023-04
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.202200229
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Article ; Online: Easy Stress Relief by EZH2.

Prasanth, Supriya G / Prasanth, Kannanganattu V

Cell

2016 Volume 167, Issue 7, Page(s) 1678–1680

Abstract: While we are beginning to appreciate the cellular roles played by long noncoding RNAs, the function of transcripts emerging from repetitive genomic regions remains enigmatic. In this issue, Zovoilis et al. report that the polycomb protein EZH2, upon heat ...

Abstract	While we are beginning to appreciate the cellular roles played by long noncoding RNAs, the function of transcripts emerging from repetitive genomic regions remains enigmatic. In this issue, Zovoilis et al. report that the polycomb protein EZH2, upon heat shock, facilitates transcription of stress-responsive genes by inducing the degradation of the transcriptional repressor B2 repeat RNA.
MeSH term(s)	Genome ; Heat-Shock Response ; Polycomb Repressive Complex 2 ; Polycomb-Group Proteins ; RNA, Long Noncoding
Chemical Substances	Polycomb-Group Proteins ; RNA, Long Noncoding ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
Language	English
Publishing date	2016--15
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2016.11.051
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Article ; Online: DNA Damage-Induced, S-Phase Specific Phosphorylation of Orc6 is Critical for the Maintenance of Genome Stability.

Lin, Yo-Chuen / Liu, Dazhen / Chakraborty, Arindam / Macias, Virgilia / Brister, Eileen / Sonalkar, Jay / Shen, Linyuan / Mitra, Jaba / Ha, Taekjip / Kajdacsy-Balla, Andre / Prasanth, Kannanganattu V / Prasanth, Supriya G

Molecular and cellular biology

2023 Volume 43, Issue 4, Page(s) 143–156

Abstract: The smallest subunit of the human Origin Recognition Complex, hOrc6, is required for DNA replication progression and plays an important role in mismatch repair (MMR) during S-phase. However, the molecular details of how hOrc6 regulates DNA replication ... ...

Abstract	The smallest subunit of the human Origin Recognition Complex, hOrc6, is required for DNA replication progression and plays an important role in mismatch repair (MMR) during S-phase. However, the molecular details of how hOrc6 regulates DNA replication and DNA damage response remain to be elucidated. Orc6 levels are elevated upon specific types of genotoxic stress, and it is phosphorylated at Thr229, predominantly during S-phase, in response to oxidative stress. Many repair pathways, including MMR, mediate oxidative DNA damage repair. Defects in MMR are linked to Lynch syndrome, predisposing patients to many cancers, including colorectal cancer. Orc6 levels are known to be elevated in colorectal cancers. Interestingly, tumor cells show reduced hOrc6-Thr229 phosphorylation compared to adjacent normal mucosa. Further, elevated expression of wild-type and the phospho-dead forms of Orc6 results in increased tumorigenicity, implying that in the absence of this "checkpoint" signal, cells proliferate unabated. Based on these results, we propose that DNA-damage-induced hOrc6-pThr229 phosphorylation during S-phase facilitates ATR signaling in the S-phase, halts fork progression, and enables assembly of repair factors to mediate efficient repair to prevent tumorigenesis. Our study provides novel insights into how hOrc6 regulates genome stability.
MeSH term(s)	Humans ; Phosphorylation ; Origin Recognition Complex/genetics ; Origin Recognition Complex/metabolism ; S Phase ; DNA Replication ; Genomic Instability ; DNA Damage
Chemical Substances	Origin Recognition Complex ; ORC6 protein, human
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1080/10985549.2023.2196204
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Article ; Online: Monoallelically expressed noncoding RNAs form nucleolar territories on NOR-containing chromosomes and regulate rRNA expression.

eLife

2024 Volume 13

Abstract: Out of the several hundred copies ... ...

Abstract	Out of the several hundred copies of
MeSH term(s)	Humans ; Animals ; Nucleolus Organizer Region/genetics ; Nucleolus Organizer Region/metabolism ; RNA Precursors/genetics ; RNA Precursors/metabolism ; Cell Nucleolus/genetics ; Cell Nucleolus/metabolism ; RNA, Ribosomal/genetics ; RNA, Ribosomal/metabolism ; Chromosomes, Human/metabolism ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; Mammals/genetics
Chemical Substances	RNA Precursors ; RNA, Ribosomal ; RNA, Untranslated
Language	English
Publishing date	2024-01-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.80684
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Article ; Online: BEND3 mediates transcriptional repression and heterochromatin organization.

Khan, Abid / Prasanth, Supriya G

Transcription

2015 Volume 6, Issue 5, Page(s) 102–105

Abstract: Transcription repression plays a central role in gene regulation. Transcription repressors utilize diverse strategies to mediate transcriptional repression. We have recently demonstrated that BEND3 (BANP, E5R and Nac1 domain) protein represses rDNA ... ...

Abstract	Transcription repression plays a central role in gene regulation. Transcription repressors utilize diverse strategies to mediate transcriptional repression. We have recently demonstrated that BEND3 (BANP, E5R and Nac1 domain) protein represses rDNA transcription by stabilizing a NoRC component. We discuss the role of BEND3 as a global regulator of gene expression and propose a model whereby BEND3 associates with chromatin remodeling complexes to modulate gene expression and heterochromatin organization.
MeSH term(s)	Cell Line ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/metabolism ; DNA, Ribosomal/metabolism ; Gene Expression Regulation ; Heterochromatin/metabolism ; Humans ; Repressor Proteins/metabolism ; Transcription, Genetic
Chemical Substances	BEND3 protein, human ; Chromosomal Proteins, Non-Histone ; DNA, Ribosomal ; Heterochromatin ; Repressor Proteins
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2646974-1
ISSN	2154-1272 ; 2154-1264
ISSN (online)	2154-1272
ISSN	2154-1264
DOI	10.1080/21541264.2015.1100228
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Article ; Online: Association of ORCA/LRWD1 with repressive histone methyl transferases mediates heterochromatin organization.

Giri, Sumanprava / Prasanth, Supriya G

Nucleus (Austin, Tex.)

2015 Volume 6, Issue 6, Page(s) 435–441

Abstract: Heterochromatin mostly constitutes tightly packaged DNA, decorated with repressive histone marks, including histone H3 methylated at lysine 9, histone H4 methylated at lysine 20 and histone H3 methylated at lysine 27. Each of these marks is incorporated ... ...

Abstract	Heterochromatin mostly constitutes tightly packaged DNA, decorated with repressive histone marks, including histone H3 methylated at lysine 9, histone H4 methylated at lysine 20 and histone H3 methylated at lysine 27. Each of these marks is incorporated by specific histone lysine methyl transferases. While constitutive heterochromatin enriched with H3K9me3 and H4K20me3 occur within repetitive elements, including centromeres and telomeres, the facultative heterochromatin resides on the inactive X-chromosome and contains H3K27me3 mark. Origin recognition complex-associated (ORCA/LRWD1) protein is required for the initiation of DNA replication and also plays crucial roles in heterochromatin organization. ORCA associates with constitutive and facultative heterochromatin in human cells and binds to repressive histone marks. We demonstrate that ORCA binds to multiple repressive histone methyl transferases including G9a, GLP, Suv39h1 (H3K9me2/3), Suv420h1/h2 (H4K20me2/3) and EZH2 (H3K27me3). Removal of ORCA from human cells causes aberrations in the chromatin architecture. We propose that ORCA acts as a scaffold protein that enables the formation of multiple histone lysine methyltransferase complexes at heterochromatic sites thereby facilitating chromatin organization.
MeSH term(s)	Adaptor Proteins, Signal Transducing/chemistry ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Cell Line, Tumor ; Chromosomes, Human, X ; DNA/chemistry ; DNA/metabolism ; DNA Methylation ; Gene Silencing ; Heterochromatin/chemistry ; Heterochromatin/metabolism ; Histone-Lysine N-Methyltransferase/metabolism ; Histones/chemistry ; Histones/metabolism ; Humans ; Microtubule Proteins/chemistry ; Microtubule Proteins/metabolism ; Models, Molecular ; Protein Binding ; Sequestosome-1 Protein
Chemical Substances	Adaptor Proteins, Signal Transducing ; Heterochromatin ; Histones ; LRWD1 protein, human ; Microtubule Proteins ; SQSTM1 protein, human ; Sequestosome-1 Protein ; DNA (9007-49-2) ; histone methyltransferase (EC 2.1.1.-) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43)
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2619626-8
ISSN	1949-1042 ; 1949-1034
ISSN (online)	1949-1042
ISSN	1949-1034
DOI	10.1080/19491034.2015.1102814
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