Condensin I Recruitment to Base Damage-Enriched DNA Lesions Is Modulated by PARP1

Kong, Xiangduo; Stephens, Jared P.; Ball, Alexander R.; Heale, Jason T.; Newkirk, Daniel A.; Berns, Michael W.; Yokomori, Kyoko

doi:10.1371/journal.pone.0023548

Cited by 31 publications

(33 citation statements)

References 26 publications

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“…1 ) [ 10 ]. Consistent with this, another major SMC proteincontaining complex, condensin I , which interacts with PARP1 and a subset of BER factors and participates in BER/SSB repair in human cells [ 15 ], is also preferentially recruited to high input-power [ 12 ] (Fig. 1 ).…”

Section: Introductionsupporting

confidence: 52%

The Use of Laser Microirradiation to Investigate the Roles of Cohesins in DNA Repair

Kong

Ball

Yokomori

2016

Methods in Molecular Biology

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In addition to their mitotic and transcriptional functions, cohesin plays critical roles in DNA damage response (DDR) and repair. Specifi cally, cohesin promotes homologous recombination (HR) repair of DNA double-strand breaks (DSBs), which is conserved from yeast to humans, and is a critical effector of ATM/ATR DDR kinase-mediated checkpoint control in mammalian cells. Optical laser microirradiation has been instrumental in revealing the damage site-specifi c functions of cohesin and, more recently, uncovering the unique role of cohesin-SA2, one of the two cohesin complexes uniquely present in higher eukaryotes, in DNA repair in human cells. In this review, we briefl y describe what we know about cohesin function and regulation in response to DNA damage, and discuss the optimized laser microirradiation conditions used to analyze cohesin responses to DNA damage in vivo.

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Section: Introductionsupporting

confidence: 52%

The Use of Laser Microirradiation to Investigate the Roles of Cohesins in DNA Repair

Kong

Ball

Yokomori

2016

Methods in Molecular Biology

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“…We attempted to identify which cohesin subunit may be responsible for directing cohesin recruitment to damage sites. For example, for condensin I, another SMC complex, we found that the chromosome-targeting domain in the hCAP-D2 subunit possesses damage site targeting activity (36). Thus, we first determined the effect of depletion of one cohesin subunit on the recruitment of other subunits in the complex.…”

Section: Resultsmentioning

confidence: 99%

“…Laser damage induction and image analysis were carried out essentially as described previously (35,36). In brief, 532 nm of the second harmonic of a pulsed Nd:YAG laser beam (ϳ2 to 3 J/pulse energy after objective; ϳ4-to 6-ns pulse duration; 7.5 Hz; Quantronix-Continuum Lasers, La Mesa, CA) was focused through a 100ϫ Ph3 UPlanFI oil objective lens (numerical aperture [NA], 1.3; Olympus) on a microscope (model IX81; Olympus).…”

Section: Methodsmentioning

confidence: 99%

Distinct Functions of Human Cohesin-SA1 and Cohesin-SA2 in Double-Strand Break Repair

Kong

Ball

Pham

et al. 2014

Molecular and Cellular Biology

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Cohesin is an essential multiprotein complex that mediates sister chromatid cohesion critical for proper segregation of chromosomes during cell division. Cohesin is also involved in DNA double-strand break (DSB) repair. In mammalian cells, cohesin is involved in both DSB repair and the damage checkpoint response, although the relationship between these two functions is unclear. Two cohesins differing by one subunit (SA1 or SA2) are present in somatic cells, but their functional specificities with regard to DNA repair remain enigmatic. We found that cohesin-SA2 is the main complex corecruited with the cohesin-loading factor NIPBL to DNA damage sites in an S/G 2 -phase-specific manner. Replacing the diverged C-terminal region of SA1 with the corresponding region of SA2 confers this activity on SA1. Depletion of SA2 but not SA1 decreased sister chromatid homologous recombination repair and affected repair pathway choice, indicating that DNA repair activity is specifically associated with cohesin recruited to damage sites. In contrast, both cohesin complexes function in the intra-S checkpoint, indicating that cell cyclespecific damage site accumulation is not a prerequisite for cohesin's intra-S checkpoint function. Our findings reveal the unique ways in which cohesin-SA1 and cohesin-SA2 participate in the DNA damage response, coordinately protecting genome integrity in human cells. DNA double-strand breaks (DSBs) are deleterious to genome integrity and can result in chromosomal breakage or translocations and cell death. The two major mechanisms to repair DSBs are the error-prone nonhomologous end joining (NHEJ) and the error-free homologous-recombination (HR) pathways, which involve distinct sets of repair proteins (1). While NHEJ operates throughout the cell cycle, HR utilizes an intact sister chromatid as a repair template and thus is restricted to S/G 2 phase in mammalian cells. Although the two pathways complement one another, the error-free HR pathway is particularly important for accurate damage repair. DSBs also evoke DNA damage checkpoint responses that are mediated by ATM (and the related ATR) (1-3). The G 1 /S and G 2 /M checkpoints, which inhibit cell cycle progression, and the intra-S checkpoint, which inhibits DNA replication, together provide adequate time for DNA repair. Both the checkpoint and the repair functions coordinately maintain genome integrity and stability.The primary function of cohesin is to mediate genome-wide sister chromatid cohesion in a cell cycle-regulated manner to ensure proper segregation of chromosomes in mitosis (4-8). Cohesin contains two SMC proteins (SMC1 and SMC3) and the two non-SMC subunits Rad21 (Scc1) and SA (Scc3 or STAG). Whereas a single Scc3 is present in yeast, two SA proteins, SA1 and SA2, are found in higher eukaryotes that form two distinct cohesin complexes in somatic cells: cohesin-SA1 and cohesin-SA2 (9, 10). Both cohesin-SA1 and cohesin-SA2 contribute to genome-wide sister chromatid cohesion, although SA1 is particularly important for telomeric sister chrom...

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“…An independent study using HeLa cells reported that condensin I is involved in DNA single-strand break (SSB) repair, possibly through its interaction with poly(ADP-ribose) polymerase 1 (PARP-1) and the base excision repair factor XRCC1 (Heale et al 2006). PARP-1 appears to contribute to the retention, but not the initial recruitment, of condensin I to DNA damage sites (Kong et al 2011).…”

Section: Dna Damage Response and Repairmentioning

confidence: 99%

Condensins: universal organizers of chromosomes with diverse functions

2012

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Condensins are multisubunit protein complexes that play a fundamental role in the structural and functional organization of chromosomes in the three domains of life. Most eukaryotic species have two different types of condensin complexes, known as condensins I and II, that fulfill nonoverlapping functions and are subjected to differential regulation during mitosis and meiosis. Recent studies revealed that the two complexes contribute to a wide variety of interphase chromosome functions, such as gene regulation, recombination, and repair. Also emerging are their cell type- and tissue-specific functions and relevance to human disease. Biochemical and structural analyses of eukaryotic and bacterial condensins steadily uncover the mechanisms of action of this class of highly sophisticated molecular machines. Future studies on condensins will not only enhance our understanding of chromosome architecture and dynamics, but also help address a previously underappreciated yet profound set of questions in chromosome biology.

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Condensin I Recruitment to Base Damage-Enriched DNA Lesions Is Modulated by PARP1

Cited by 31 publications

References 26 publications

The Use of Laser Microirradiation to Investigate the Roles of Cohesins in DNA Repair

The Use of Laser Microirradiation to Investigate the Roles of Cohesins in DNA Repair

Distinct Functions of Human Cohesin-SA1 and Cohesin-SA2 in Double-Strand Break Repair

Condensins: universal organizers of chromosomes with diverse functions

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